The Adolescent Brain and the College Drinker: Biological Basis of Propensity
to Use and Misuse Alcohol*
LINDA PATIA SPEAR, Ph.D.
Department of Psychology and Center for Developmental Psychobiology, Binghamton
University, Binghamton, New York 13902-6000
ABSTRACT. Objective: This article reviews the literature on adolescent
brain development and considers the impact of these neural alterations on the
propensity to use and misuse alcohol. Method: Neural, behavioral and
hormonal characteristics of adolescents across a variety of species were examined,
along with a review of the ontogeny of ethanol responsiveness, tolerance development
and stress/alcohol interactions. Results: The adolescent brain is a brain
in transition. Prominent among the brain regions undergoing developmental change
during adolescence in a variety of species are the prefrontal cortex and other
forebrain dopamine projection regions, stressor-sensitive areas that form part
of the neural circuitry modulating the motivational value of alcohol and other
reinforcing stimuli. Along with these characteristic brain features, adolescents
also exhibit increased stressor responsivity and an altered sensitivity to a
variety of ethanol effects. Findings are mixed to date as to whether exposure
to ethanol during this time of rapid brain development alters neurocognitive
function and later propensity for problematic ethanol use. Conclusions:
Developmental transformations of the adolescent brain may have been evolutionarily
advantageous in promoting behavioral adaptations to avoid inbreeding and to
facilitate the transition to independence. These brain transformations may also
alter sensitivity of adolescents to a number of alcohol effects, leading perhaps
in some cases to higher intakes to attain reinforcing effects. These features
of the adolescent brain may also increase the sensitivity of adolescents to
stressors, further escalating their propensity to initiate alcohol use. Additional
investigations are needed to resolve whether ethanol use during adolescence
disrupts maturational processes in ethanol-sensitive brain regions. (J. Stud.
Alcohol, Supplement No. 14: 71-81, 2002)
TO NEGOTIATE with success the developmental transition from youth to maturity,
adolescents of many species must survive the risks and stresses of this passage
while obtaining the skills necessary for independence. Although certain attributes
of human adolescents are unique and not evident in other species, other characteristic
features are expressed by adolescents of diverse species and may have been evolutionarily
adaptive in helping adolescents conquer this critical transition.
Characteristics of Adolescence
in Humans and Other Animals
The process of adolescence is not synonymous with puberty.
Adolescence includes the entire transition from childhood
to adulthood; puberty is a more discrete phase during
which the physiological and neuroendocrine alterations associated
with sexual maturation occur. Puberty is only one
of the ontogenetic alterations occurring during adolescence,
with the timing of this phase within the broader framework
of adolescence varying notably among human adolescents
(e.g., Dubas, 1991).
The temporal boundaries of adolescence are elusive. It
is difficult in any species to characterize when the first
transition of adolescence begins to emerge and the last remnant
still persists. In humans, adolescence is commonly defined
as the second decade of life (Petersen et al., 1996),
with ages up to 25 years considered late adolescence by
some researchers (Baumrind, 1987). In rats, commonly cited
times for the onset of adolescence are postnatal days 28-32
(P28-32), with offsets between P38-55 (e.g., Ojeda and
Urbanski, 1994), although this timing is somewhat disputed
(Odell, 1990) and may depend on growth rate (Kennedy
and Mitra, 1963). Spear and Brake (1983) operationally
defined “periadolescence” as the age period around the time
of sexual maturation when age-specific behavioral and psychopharmacological
discontinuities were evident. Using this
criterion, the age period of approximately P28-42 in rats
was conservatively designated as periadolescence, with animals
of this age showing numerous neurobehavioral alterations
from significantly younger (pre- or postweanling)
animals as well as more mature (P60 and older) animals.
Adolescence in monkeys typically occurs in the age range
of 2-4 years (see Lewis, 1997).
Hormonal concomitants of adolescence
Puberty represents a reactivation, after a prolonged period
of suppression during the childhood/juvenile period,
of pulsatile release of gonadotropin-releasing hormone that
was evident perinatally. This reinstatement of pulsatile release
of gonadotropin-releasing hormone induces pulsed
release of follicle-stimulating hormone and luteinizing hormone,
which in turn stimulate release of gonadal hormones
(e.g., testosterone in males and estrogen in females) (e.g.,
Brooks-Gunn and Reiter, 1990). Pulsatile release of growth
hormone also increases more than 10-fold during the growth
spurt of adolescence (Gabriel et al., 1992). Surprisingly,
many of the characteristic behavioral features of adolescence
discussed below do not seem to be associated in any
simple fashion with puberty-related increases in gonadal
hormones (e.g., Susman et al., 1987), but rather may be
driven largely by maturational changes in the nervous system
(reviewed in a later section; see also Spear, 2000).
Behavioral characteristics of adolescence
Adolescents of a variety of species differ behaviorally
from younger and older individuals on a number of dimensions
consistent with a developmental trajectory toward the
goal of independence. Adolescent rats exhibit increases in
exploration and novelty seeking relative to other aged rats
(e.g., Spear et al., 1980; for review, see Spear, 2000). They
also spend more time in social interactions with conspecifics
(Fassino and Campbell, 1981; Primus and Kellogg,
1989). Sex differences in behavior also begin to emerge in
adolescence, with some of these differences being driven
in part by organizational influences of pubertal hormones
(e.g., Beatty and Fessler, 1977; Brand and Slob, 1988).
Human adolescents likewise exhibit increases in social behavior
(Csikszentmihalyi et al., 1977), as well as a disproportionate
amount of reckless behavior, sensation seeking
and risk taking relative to individuals at other ages (Arnett,
1992). Together such age-related modifications in behavior
are consistent with the need of the adolescent to explore
novel domains and establish new social relationships during
the process of achieving parental independence. Across
most mammalian species, adolescence is associated with
emigration of male and/or female adolescents away from
the natal group into unknown territory, a strategy thought
to have been evolutionarily advantageous for species to
avoid the detrimental effects of inbreeding (e.g., see Schlegel
and Barry, 1991).
Adolescents also seemingly exhibit age-related alterations
in the way they respond to motivational stimuli. Human
adolescents exhibit an increase in negative affect and depressed
mood relative to younger or older individuals (e.g.,
Larson and Asmussen, 1991). In addition to greater negative
affect, adolescents seemingly experience and expect to
experience positive situations as less pleasurable than
younger or older individuals. Between late childhood and
adolescence, the number of reports of feeling happy drops
by 50%; even when engaged in the same activities, adolescents
find them less pleasurable than do adults (Larson and
Richards, 1994). Thus human adolescents appear to show
some degree of anhedonia, seeming to attain less positive
impact from stimuli with moderate to low incentive value.
As a consequence, adolescents may be predisposed to pursue
new appetitive reinforcers through increases in risk taking
and novelty-seeking behaviors, including alcohol and
In animal studies, adolescents also have been shown to
exhibit characteristic alterations in psychopharmacological
sensitivity suggestive of a temporary hyposensitivity of one
or more dopamine (DA) systems during adolescence. For
example, adolescent rats are less sensitive than their younger
or older counterparts to the acute stimulatory effects of catecholaminergic
agonists such as amphetamine and cocaine,
but conversely are more sensitive to the DA antagonist haloperidol
(for references and discussion, see Spear and
Brake, 1983). Indeed, alterations in mesocorticolimbic DA
systems are a particular hallmark of the adolescent brain,
as discussed in the next section.
Neural alterations during adolescence
The adolescent brain is unique and in a state of transition
as it undergoes both progressive and regressive changes
(for review, see Spear, 2000). One brain region prominently
altered during adolescence across a variety of species is the
prefrontal cortex, an area thought to subserve higher cognitive
abilities such as the bridging of temporal delays in
memory (e.g., Diamond, 1991). For example, absolute prefrontal
cortex volume declines in adolescence in humans
(Jernigan et al., 1991) as well as in rats (van Eden et al.,
1990). Substantial synapse elimination occurs during adolescence
in the prefrontal cortex and other cortical regions
in humans (Huttenlocher, 1984) and in nonhuman primates
(Zecevic et al., 1989). At least a portion of this synapse
elimination in the prefrontal cortex appears to be associated
with the marked developmental loss of presumed
glutaminergic excitatory input (Zecevic et al., 1989). In contrast,
DA input to the prefrontal cortex in nonhuman primates
increases during adolescence to peak at levels well
above those seen earlier or later in life (Rosenberg and
Lewis, 1994; for review, see Lewis, 1997). Increases in
prefrontal cortex DA input through adolescence are also
evident in rats (Kalsbeek et al., 1988). Cholinergic innervation
of the prefrontal cortex likewise increases in adolescence
to reach mature levels in rats (Gould et al., 1991)
and humans (Kostovic, 1990).
Maturational changes during adolescence are also evident
in other brain regions such as the hippocampus of
rodents (Dumas and Foster, 1998; Wolfer and Lipp, 1995)
and humans (Benes, 1989). Alterations evident in the hypothalamus
include qualitative differences in norepinephrine
(NE) release evident in adolescents relative to younger
or older rats, along with pharmacological alterations consistent
with the suggested emergence in adolescence of inhibitory
alpha-2 NE autoreceptors (Choi and Kellogg, 1992;
Choi et al., 1997).
Dopaminergic systems undergo substantial reorganization during adolescence.
More than one-third to one-half of the DA D1 and D2 receptors
present in the striatum of juveniles are lost by adulthood in both humans (Seeman
et al., 1987) and rats (Gelbard et al., 1989; Teicher et al., 1995). This peak
in D1 and D2 binding during adolescence and subsequent
decline is much more pronounced in the striatum than in the nucleus accumbens
(Teicher et al., 1995) and in male rats than in female rats (Andersen et al.,
1997b). Not all DA receptors show this overproduction and pruning, with juveniles
having only 40% of adult-typical DA D3 receptor levels in striatal
and accumbens regions (Stanwood et al., 1997). The DA transporter likewise undergoes
a protracted period of development in mesolimbic and mesocortical brain regions,
with only about 70% of adult uptake levels being seen prior to adolescence onset
in rats (Coulter et al., 1996).
Developmental events during adolescence may alter the
relative balance of DA activity between the prefrontal cortex
and striatal or mesolimbic terminal regions, resulting in
a greater predominance of DA activity in the prefrontal
cortex during early adolescence. As mentioned previously,
DA input to the prefrontal cortex increases during adolescence
in nonhuman primates (Rosenberg and Lewis, 1994)
and rats (Kalsbeek et al., 1988). Basal DA synthesis peaks
in rat prefrontal cortex early in adolescence and subsequently
wanes, while synthesis is low at this time in nucleus
accumbens and subsequently increases (Andersen et al.,
1997a). Similar data are obtained from estimates of DA
turnover (Teicher et al., 1993). Interestingly, although the
prefrontal cortex is seemingly devoid of synthesis-modulating
autoreceptors in adulthood (e.g., Galloway et al.,
1986), convincing evidence has been obtained for a transient
expression of DA autoreceptor-like modulation of DA
synthesis in the prefrontal cortex early in life that disappears
during adolescence (Andersen et al., 1997a; Teicher
et al., 1991).
A shift in the balance of DA activity from the nucleus
accumbens to the prefrontal cortex early in adolescence
would seemingly result in a relative DA deficiency at this
time in the accumbens, a mesolimbic brain region critical
for modulating the salience of various incentive stimuli,
including alcohol and other drugs of misuse (e.g., Koob,
1992). Functional DA deficits in the accumbens and related
mesolimbic brain regions have been linked to a reward
deficiency syndrome. Individuals with this syndrome
have been postulated to “actively seek out not only addicting
drugs but also environmental novelty and sensation as
a type of behavioral remediation of reward deficiency”
(Gardner, 1999, p. 82). It remains to be determined whether
adolescents, because of age-related shifts in the balance of
DA activity among mesocorticolimbic brain regions, might
show a transient “reward deficiency syndrome” that is milder
although qualitatively similar to that hypothesized to be
characteristic of abstinent drug users and other at-risk adults.
Consistent with this speculation is evidence (previously discussed)
that human adolescents show signs of anhedonia,
as well as findings that adolescent animals exhibit a reduced
sensitivity to certain effects of drugs such as alcohol
when compared with their adult counterparts (see discussion
Clearly, the brain of the adolescent is in transition. Neural
regions showing prominent alterations during adolescence
include the prefrontal cortex as well as other forebrain
DA projection regions. Given the importance of these brain
areas in modulating reward efficacy of reinforcing drugs
(Koob, 1992), sensitivity to the environment and stressors
(e.g., Dunn and Kramarcy, 1984) and the association between
the two (e.g., Goeders, 1997; Piazza et al., 1991), it
is not surprising that adolescents vary notably from more
mature animals in their responsivity to ethanol, stressors
and their interaction, as discussed in the sections below.
Ontogeny of Responsivity to Ethanol
Prevalence of alcohol use in adolescents
In the 2000 Monitoring the Future Survey of the National
Institute on Drug Abuse (Johnston et al., 2001), 43%
of 8th graders, 65% of 10th graders and 73% of high school
seniors reported that they had used alcohol in the past year.
About 8% of 8th graders, 24% of 10th graders and 32% of
12th graders also reported getting drunk on one or more
occasions during the past month. Clearly, many adolescents
use alcohol, with evidence of excessive use emerging in
Adolescents are not immune to the development of dependence
and may exhibit a variety of alcohol dependence
symptoms, including evidence of ethanol tolerance, escalated
patterns of use and difficulty in cutting down or quitting
(Pollock and Martin, 1999). Once adolescents become
dependent on alcohol, their rates of relapse approximate
those of alcoholic adults, despite the much shorter chronicity
of alcohol use in the adolescent (Brown, 1993). Escalation
of alcohol use may be unusually rapid during
adolescence. Compared with individuals initiating drug use
in adulthood, adolescent-onset individuals had “accelerated
dependency courses, with shorter times from first exposure
to dependence for alcohol and cannabis and shorter times
between their first and second dependencies” (Clark et al.,
1998, p. 120).
Adolescent rats display two to three times higher levels
of ethanol intake relative to their body weights than do
more mature animals (Brunell et al., 2001; Lancaster et al.,
1996), although ethanol preference per se does not peak
until well into adulthood (around 5 months of age [Goodrick,
1967; Parisella and Pritham, 1964]). The notably different
ontogenetic conclusions reached when using gram-per-
kilogram intake versus percentage of total fluid to index
ethanol consumption seemingly reflect ontogenetic differences
in total fluid consumption, with adolescent rats exhibiting
greater overall fluid (and food) consumption than
adults. Indeed, during the adolescent growth spurt, caloric
intake relative to body weight is greater than at any other
time in the life span (e.g., Nance, 1983). Adolescent humans
also exhibit elevated metabolic activity and developmental
hyperphagia (e.g., Ganji and Betts, 1995; Post and
Kemper, 1993), with heavy alcohol use often being
“adolescence-limited” (e.g., Bates and Labouvie, 1997).
The elevated consummatory patterns of adolescence
could contribute to high levels of ethanol intake by these
growing individuals relative to their body weight. As discussed
below, adolescents might be able to sustain comparatively
large ethanol intakes due to their relative
insensitivity to the sedative and locomotor incoordinating
effects of ethanol, which may be in part related to their
greater propensity to develop acute and functional tolerance
relative to more mature organisms.
Acute responsivity to alcohol
Studies using a variety of measures in laboratory animals
have observed increases in ethanol sensitivity from
infancy through adolescence and into adulthood, with further
increases in sensitivity during the aging process (e.g.,
York and Chan, 1993). This early insensitivity to many
ethanol effects is evident despite slower rates of ethanol
metabolism in younger animals (e.g., Silveri and Spear,
2000; Zorzano and Herrera, 1989) and is evident using measures
such as lethal dose (Hollstedt and Rydberg, 1985),
motor impairment (Hollstedt et al., 1980; Moy et al., 1998),
hypothermia (Silveri and Spear, 2001; Spiers and Fusco,
1991), anxiolytic effects (Varlinskaya and Spear, 2001) and
ethanol-induced hypnosis (Ernst et al., 1976; Little et al.,
1996; Silveri and Spear, 1998). These findings, however,
are not ubiquitous (e.g., Keir and Deitrich, 1990).
Whether a similar insensitivity to various ethanol effects
is evident prior to maturity in humans is unknown,
with research in this area limited by ethical constraints.
Even if it were possible to conduct controlled studies of
ethanol responsivity in children and adolescents, interpretation
of across-age data would be complicated by issues such
as history of prior use, ethanol tolerance and intoxicated
practice effects. On the one hand, it could be argued that
an adolescent insensitivity to ethanol effects would be inconsistent
with the high incidence of morbidity and mortality
during adolescence (Irwin and Millstein, 1992) due in
part to risk behaviors involving alcohol use (e.g., drinking
and driving) (Donovan, 1993). On the other hand, a relative
insensitivity to ethanol effects could contribute to the
high incidence of heavy episodic drinking among adolescents.
In the year 2000 data from the Monitoring the Future
Study, 14.1% of 8th graders, 26.2% of 10th graders
and 30.0% of 12th graders reported drinking five or more
drinks in a row within the past 2 weeks. Surprisingly, these
percentages at the two younger ages were higher than those
reporting drunkenness, with only 8.3% of 8th graders and
23.5% of 10th graders indicating that they were drunk on
one or more occasions during the past month (comparable
data for 12th graders was 32.3%). To the extent that these
data are accurate, fewer young to mid-adolescents reported
being drunk than drinking five or more drinks in a row,
findings consistent with a relative insensitivity to ethanol
intoxication among younger adolescents when compared
with more mature individuals. Alternatively, these survey
data could reflect inflation of alcohol consumption or inaccuracies
in perception or reporting of intoxication among
Although studies using animal models have documented
that adolescents are resistant to many ethanol effects, they
are conversely more sensitive to certain restricted effects
of ethanol-specifically ethanol-induced disruptions of hippocampal
plasticity and memory. Swartzwelder et al.
(1995a,b) found that hippocampal slices from preadolescent
(P15-25) rats were more sensitive than adult slices to
ethanol disruption of both N-methyl-D-aspartate (NMDA)-
mediated excitation as well as stimulus-induced long-term
potentiation. Behaviorally, P30 adolescent rats were found
to be more impaired than adult rats by ethanol in a
hippocampally related spatial memory task in the Morris
maze, whereas nonspatial performance was unaffected by
ethanol at either age (Markwiese et al., 1998). Somewhat
similar age-related memory disruptions by ethanol have been
reported in humans, with early postadolescent (21- to 24-
year old) adults showing more ethanol-induced disruption
of memory acquisition on both semantic and figural memory
tasks than slightly older (25- to 29-year old) individuals
(Acheson et al., 1998). Thus, although reduced sensitivity
to motor impairing, anxiolytic and sedative consequences
of ethanol (see above) may permit adolescents to consume
greater amounts of ethanol, this exposure may have more
adverse effects on hippocampally related memory processing
than later in life.
Taken together, the animal data show that the mosaic of
behavioral sensitivities to different ethanol effects vary between
adolescents and adults, with adolescents showing
greater sensitivity to ethanol-induced impairments of cognitive
performance and long-term potentiation, but less sensitivity
to ethanol-related sedative, motor impairment and
anxiolytic effects. These divergent patterns of sensitivities
may represent differential development of neural systems
underlying different cognitive and behavioral consequences
of ethanol. For example, although ethanol-induced disruption
of spatial memory appears to be linked to developmental
changes in hippocampal glutamate/NMDA systems
(see Swartzwelder et al., 1995a,b), developmental immaturity
in brain gamma-aminobutyric acid (GABA) systemsrather than
ontogenetic alterations in NMDA systems appears to
contribute in part to the lower sensitivity of adolescent
animals to the sedative effects of ethanol (Moy et
al., 1998; Silveri and Spear, in press).
Differential sensitivity to various ethanol effects between
adolescents and adults may also be attributable in part to
possible ontogenetic differences in the capacity to develop
ethanol tolerance. For example, the resistance of young organisms
to ethanol's hypnotic effects has been shown to be
related in part to the tolerance that develops within a given
ethanol exposure period. This form of within-session tolerance
is called acute tolerance and is very prevalent early in
life, declining to reach adult levels only during late adolescence
(Silveri and Spear, 1998). This ontogenetic decline
may be specific to acute tolerance, with forms of tolerance
that emerge only following repeated ethanol exposures
showing different ontogenetic patterns. For example, Silveri
and Spear (1999) reported that preweanling and adolescent
rats showed no evidence of rapid tolerance (tolerance developing
with 24-48 hours after repeated ethanol exposures)
to ethanol-induced sleep, whereas such tolerance was evident
in adults. On the other hand, following multiple ethanol
exposures, adolescents have been reported to exhibit
more chronic tolerance to ethanol-induced hypothermia than
adult rats (Swartzwelder et al., 1998). The sometimes greater
propensity for adolescent animals to develop these compensatory
adaptations to ethanol may contribute to their
relative resistance to many ethanol effects relative to their
more mature counterparts. Yet it remains to be determined
whether similar adaptations would be evident in human adolescents.
Empirical research of this nature would be difficult
to conduct given ethical constraints on exposing human
children and adolescents to ethanol even on a single occasion,
let alone repeatedly.
Stress, Adolescence and Alcohol Misuse
Stress and adolescence
Navigating the developmental transition toward independence
is often stressful for human adolescents, and indeed
adolescents appear to experience a greater number of negative
life events than preadolescents (Larson and Asmussen,
1991). In addition to the actual frequency of life stressors
possibly being greater in adolescence than at other ages,
adolescents may also respond differently to stress than individuals
at other ages. This perhaps should not be surprising,
given that stressors selectively activate many of the
neural systems undergoing developmental change during
adolescence (for review, see Spear, 2000), including
mesocorticolimbic DA projections implicated in modulating
the reward value of drugs (Dunn and Kramarcy, 1984).
In general, adolescents appear to respond with greater
negative affect to circumstances in their environment than
do children and adults (Larson and Richards, 1994). They
also typically find the circumstances of their lives to be
more anxiety provoking and stressful. For example, using
electronic diaries to monitor moods and certain behaviors
of 14-year olds, Whalen et al. (2001) found that even adolescents
who scored low on externalizing and depression
measures reported feeling anxious more than one-third of
the time and stressed about 25% of the time.
In behavioral studies with laboratory animals, adolescents
often have been observed to be more susceptible to
stressors than adults. For example, adolescent rats show
more stress-induced immobility during forced swim testing
(Walker et al., 1995) or in the presence of intermittent footshock
(Campbell et al., in preparation) than do adults. As
another example, Stone and Quartermain (1997) found that
chronic exposure to social stress (placement in the cage of
an isolated adult male for 5 minutes daily for 5 days) or a
daily period of restraint stress had a greater impact on adolescent
mice (P28-32) than on adult male mice, suppressing
food intake and body weight gain in adolescents but
not adults. In this study, the chronic social stress was also
observed to increase anxiety (indexed by a suppression of
time spent on the open arms of an elevated plus maze) in
the adolescents but not the adult mice.
Exposure to a stressor activates the hypothalamicpituitary-
adrenal (HPA) axis, resulting in a cascading
sequence of hormone release from the hypothalamus
(corticotropin-releasing factor), pituitary (adrenocorticotropic
hormone [ACTH]) and adrenals (corticosterone in rats;
cortisol in humans). Whereas some research has reported
that there are developmental increases in HPA activity
through adolescence in humans (Kiess et al., 1995), the
ontogeny of stress-induced activation of the HPA system
and associated neurobehavioral consequences has been most
systematically examined in laboratory animals. Peak ACTH
and corticosterone responses to stress generally increase during
ontogeny to reach an asymptote in rats around adolescence,
at least in males (Bailey and Kitchen, 1987; Meaney
et al., 1985a; Ramaley and Olson, 1974; Rivier, 1989;
Walker et al., 1986). Adolescent rats have also been reported
to exhibit more prolonged stress-induced increases
in corticosterone than adults (Choi and Kellogg, 1996;
Goldman et al., 1973; Sapolsky et al., 1985). This delayed
poststress recovery presumably reflects immature feedback
regulation mediated in part by glucocorticoid receptors in
the hippocampus (e.g., Meaney et al., 1985a,b). Thus adolescence
may be associated with a greater overall corticoid
response to stress, with this stress-induced increase being
elevated relative to younger animals and prolonged relative
Although little explored, the nervous system also appears
to respond differently to stressors during adolescence
than at younger or older ages. For example, Choi and
Kellogg (1996) observed a blunted hypothalamic NE response
to stress in late adolescent rats (P42), a transition
between the increased stress-related NE utilization seen in
early adolescence (P28) and the decreased utilization seen
in adulthood. A similar adolescent transitional period was
seen in terms of autonomic reactivity to stressor stimuli in
the peripheral nervous system. Whereas preweanling rat
pups exhibited heart rate bradycardia to an aversive stimulus,
heart rate tachycardia emerged by adolescence, with
this increased heart rate mediated by parasympathetic withdrawal
in adolescents but primarily by sympathetic activation
in adults (Kurtz and Campbell, 1994).
Thus, along with the presumed increase in the number
of stressors to which adolescents are exposed as they navigate
this critical developmental transition, the way adolescents
respond to stressors may vary hormonally, behaviorally
and neurally from that of other aged organisms.
Stress and alcohol consumption in adolescents
The apparent increase in the number of stressors to which
adolescents are exposed and their age-typical responses to
such stressors have been postulated to contribute to the frequent
initiation of alcohol and other drug use in adolescence
(e.g., Pohorecky, 1991; Wagner, 1993) as well as to
the frequent emergence in adolescence of schizophrenic
symptomatology in vulnerable individuals (Walker and
Diforio, 1997). Indeed, alcohol use among adolescents has
been shown to be predicted by stressors such as prior abuse,
victimization and other negative life events (Kilpatrick et
al., 2000; Sussman and Dent, 2000); negative school-related
events (Unger et al., 2001); neighborhood stress
(Scheier et al., 1999); and parental conflict and peer relationship
problems (Aseltine and Gore, 2000). Coping strategies
may interact with levels of stress in predicting
alcohol-related problems (Laurent et al., 1997), with alcohol
use suggested to be one of a number of “maladaptive
ways to cope with stress” (Scharf, 1999).
Perceiving events as being stressful may be of particular
importance in exacerbating the already elevated propensity
of human adolescents to exhibit alcohol use and other drugtaking
behavior (Baer et al., 1987; Deykin et al., 1987;
Tschann et al., 1994; Wills, 1986; but see also Hansell and
White, 1991). After peer substance use, the next most powerful
predictor of adolescent alcohol and drug use was found
by Wagner (1993) to be levels of perceived stress, with the
appraisal of events as being stressful of more importance
than the absolute number of such events. Adolescents, especially
younger adolescents, may be particularly prone to
these stressor effects. In her review of the literature on
stress effects on alcohol consumption in humans, Pohorecky
(1991) concluded that stress is most convincingly associated
with alcohol consumption in adolescence, with more
mixed findings evident in studies conducted in adults. Using
a linear growth curve analysis to examine age differences
in drinking across five waves of data from a
community sample of adolescents, Aseltine and Gore (2000)
observed the strongest association between stress and drinking
among younger adolescents, with the relationship weakening
during the late teens and twenties.
Factors contributing to the stress-induced increase in propensity
for ethanol use are still being explored. Although
the interaction of stress and ethanol intake is complex (for
review, see Pohorecky, 1990), stress hormones may play a
role. Corticosterone levels in rats generally have been positively
related to rates of self-administration of ethanol or
other drugs, with adrenalectomy suppressing ethanol consumption
(Fahlke et al., 1994) and stress-induced elevations
in corticosterone increasing ethanol consumption (e.g.,
Bowers et al., 1997). Stressors may also enhance the rate
of tolerance development to ethanol (Maier and Pohorecky,
1986), thereby indirectly increasing ethanol consumption
Taken together, the data available to date support the
suggestion that the stressors of adolescence along with agespecific
neural and hormonal responses to these stressors
may contribute to the initiation of ethanol use during adolescence
and the emergence of high levels of use among
particularly stressed (or stress vulnerable) individuals.
Does Adolescent Alcohol Exposure Alter
Ongoing Processes of Brain Development?
As discussed previously, the adolescent brain is a brain
in flux. Many of the brain areas undergoing dramatic developmental
change during adolescence are sensitive to ethanol.
Ethanol use during adolescence may alter the
developmental processes ongoing in these brain regions and
hence may have different consequences than similar amounts
of ethanol exposure in adulthood. Several recent studies in
laboratory animals have supported this possibility. For example,
following a 4-day period of multiple ethanol
intubations (resulting in exposures of 9-10 g/kg/day), adolescent
rats were found to exhibit substantially more
ethanol-induced damage in brain regions including the frontal
cortex than similarly treated adults (Crews et al., 2000).
Rats exposed chronically to ethanol over a 20-day period
that included much of the adolescent period were reported
subsequently to exhibit a larger impairment in working
memory following acute ethanol challenge than adults who
were similarly exposed to ethanol (White et al., 2000). These
data extend earlier findings in rats showing long-lasting
alterations in cognitive functioning following chronic ethanol
exposure during adolescence (Osborne and Butler,
1983). Exposure to ethanol vapor for 5 or 10 days has
recently been reported to alter parietal and hippocampal
electroencephalogram activity in adolescent rats (Slawecki
et al., 2001), whereas the opportunity to consume alcohol
voluntarily during adolescence was found to increase later
aggressive behavior in male golden hamsters (Ferris et al.,
1998; Shtiegman et al., 1997). Whether similar effects would
be seen with comparable exposures later in life is unknown
in these latter studies, given the absence of adult comparison
groups. Nevertheless, it appears from the limited amount
of evidence available to date that alcohol exposure during
adolescence in laboratory animals may not only disrupt puberty
associated increases in reproductive endocrinology in
males (Cicero et al., 1990) and females (Dees et al., 1990),
but also may induce long-term alterations in neurobehavioral
function as well.
A number of studies have recently examined neurocognitive
function in human adolescents with a history of
extensive alcohol use. Adolescents with alcohol use disorders
had been reported to have smaller hippocampal volumes
than comparison subjects, with these hippocampal
volumes correlating positively with onset age and negatively
with duration of the use disorder (De Bellis et al.,
2000). Brown et al. (2000) recently observed subtle to modest
neuropsychological impairments, including memory retrieval
deficits, in alcohol dependent adolescents with a
history of heavy drinking during early and mid-adolescence.
It remains to be determined, however, whether these reported
associations between alcohol use and neuropsychological
impairments are causal and whether these findings
are relevant for nonclinical populations of adolescents. Indeed,
Bates and Tracy (1990) concluded from their assessments
of cognitive functioning in a nonclinical sample of
18- to 24-year olds that “cognitive performance bears little
direct relation to drinking behaviors in young nonclinical
males and females” (p. 242).
When considering potential long-term consequences of
adolescent alcohol use, an important issue is whether this
exposure alters later sensitivity to, and patterns of, alcohol
use. The data are mixed on this point both in studies conducted
in humans and in laboratory animals. For example,
findings in rodent studies showing that preweaning (Hayashi
and Tadokoro, 1985) or postweaning (Ho et al., 1989) exposure
to ethanol increases later ethanol preference are countered
by results from several groups reporting no increase
in later consumption following periods of ethanol exposure
that include adolescence (Kakihana and McClearn, 1963;
Parisella and Pritham, 1964; Tolliver and Samson, 1991).
Studies conducted in humans likewise present a mixed
picture. Early onset of alcohol use has been reported in
both prospective and retrospective studies to be a predictor
of later problematic use and dependence on alcohol (Barnes
and Welte, 1986; Deykin et al., 1987; Fergusson et al.,
1994; Friedman and Humphrey, 1985; Grant and Dawson,
1997; Hawkins et al., 1997; Rachal et al., 1982; Robins
and Przybeck, 1985) and other drugs (Deykin et al. 1987;
Robins and McEvoy, 1990; Robins and Przybeck, 1985;
Yamaguchi and Kandel, 1984). However, an association
between early ethanol use and later problematic use is not
always seen. For example, based on findings from four
waves of longitudinal data obtained from a nonclinical population
ranging in age from 15 to 31 years, Labouvie et al.
(1997) concluded that early use of alcohol did not predict
drug or alcohol use at either 20 or 30 years of age. Even if
early alcohol consumption is found to predict later problematic
use and dependence, it is possible that the early use
may merely be serving as a marker of later ethanol problems
rather than as a causal precursor. For example, in a
study of human twins, Prescott and Kendler (1999) reported
that the age of initiation of alcohol use was not a direct
risk factor for alcoholism, but was an “alternative manifestation
of vulnerability to problematic alcohol involvement”
Taken together, recent evidence supports the suggestion
that high amounts of alcohol exposure during adolescence
may disrupt critical ongoing processes of brain maturation
and influence neurocognitive functioning. These findings,
however, still need to be replicated and extended, and their
relevance to more moderate patterns of alcohol use determined.
Whether early exposure to alcohol during adolescence
promotes greater ethanol use and probability of
dependence later in life remains to be resolved, with mixed
findings both in studies with humans as well as in work
using animal models of adolescent alcohol exposure.
Alcohol is frequently used by adolescents prior to and
during the early college years. This age is critical for study
for several reasons. First, the brain of the adolescent is
unique and differs from that of younger individuals and
adults in numerous regions, including stressor-sensitive,
mesocorticolimbic DA projections that are critical for modulating
the perceived value of reinforcing stimuli, including
use of alcohol and other drugs. These features of adolescent
brain may predispose adolescents to behave in particular
ways, increasing their sensitivity to stressors and
their propensity to initiate alcohol use. Thus, like a number
of adolescent behaviors, the predisposition for alcohol use
may be in part biologically determined by age-specific neural
alterations that continue into late adolescence.
Certainly, given the dramatic differences between the
adolescent and the adult brain, it cannot be assumed that
factors precipitating the initiation and escalation of alcohol
use would be the same during the stressful period of adolescence
as in adulthood. Among critical areas for further
investigation is the rather paradoxical notion that adolescents
may show a reduced sensitivity to many alcohol effects,
perhaps supporting elevated intakes to attain
reinforcing effects and a potentially more rapid progression
into dependence by adolescents relative to adults. Another
important area for future inquiry is the potential long-term
consequences of alcohol use during this time of rapid neural
and endocrine maturation. It is often the case that rapidly
changing systems are particularly vulnerable to
disruption, and hence there may be unique long-term consequences
of alcohol exposure during adolescence. Data
are mixed on this point to date and further research is
Acheson, S.K., Stein, R.M. and Swartzwelder, H.S. Impairment of semantic and
figural memory by acute ethanol: Age-dependent effects. Alcsm Clin. Exp. Res.
22: 1437-1442, 1998.
Andersen, S.L., Dumont, N.L. and Teicher, M.H. Developmental differences in
dopamine synthesis inhibition By ( )-7-OH-DPAT. Naunyn- Schmiedeberg's Arch.
Pharmacol. 356: 173-181, 1997a.
Andersen, S.L., Rutstein, M., Benzo, J.M., Hostetter, J.C. and Teicher, M.H.
Sex differences in dopamine receptor overproduction and elimination. Neuroreport
8: 1495-1498, 1997b.
Arnett, J. Reckless behavior in adolescence: A developmental perspective. Devel.
Rev. 12: 339-373, 1992.
Aseltine, R.H., Jr. and Gore, S.L. The variable effects of stress on alcohol
use from adolescence to early adulthood. Subst. Use Misuse 35: 643-668,
Baer, P.E., Garmezy, L.B., McLaughlin, R.J., Pokorny, A.D. and Wernick, M.J.
Stress, coping, family conflict, and adolescent alcohol use. J. Behav. Med.
10: 449-466, 1987.
Bailey, C.C. and Kitchen, I. Developmental Responses to opioids reveals a lack
of effect on stress-induced corticosterone levels in neonatal rats. Brit. J.
Pharmacol. 91: 119-125, 1987.
Barnes, G.M. and Welte, J.W. Patterns and predictors of alcohol use among 7-12th
grade students in New York State. J. Stud. Alcohol 47: 53-62, 1986.
Bates, M.E. and Labouvie, E.W. Adolescent risk factors and the prediction of
persistent alcohol and drug use into adulthood. Alcsm Clin. Exp. Res. 21:
Bates, M.E. and Tracy, J.I. Cognitive functioning in young social drinkers.
Is there impairment to detect? J. Abnorm. Psychol. 99: 242-249, 1990.
Baumrind, D. A developmental perspective on adolescent risk taking in contemporary
America. In: Irwin, C.E., Jr. (Ed.) Adolescent Social Behavior and Health, San
Francisco, CA: Jossey-Bass, 1987, pp. 93- 125.
Beatty, W.W. and Fessler, R.G. Gonadectomy and sensitivity to electric shock
in the rat. Physiol. Behav. 19: 1-6, 1977.
Benes, F.M. Myelination of cortical-hippocampal relays during late adolescence.
Schizophren. Bull. 15: 585-593, 1989.
Bowers, W.J., Sabongui, A.G. and Amit, Z. The role of ethanol availability
on stress-induced increases in ethanol consumption. Alcohol 14: 551-556,
Brand, T. and Slob, A.K. Peripubertal castration of male rats, adult open field
ambulation and partner preference behavior. Behav. Brain Res. 30: 111-117,
Brooks-Gunn, J. and Reiter, E.O. The role of pubertal processes. In: Feldman,
S.S. and Elliott, G.R. (Eds.) At the Threshold: The Developing Adolescent, Cambridge,
MA: Harvard Univ. Press, 1990, pp. 16-53.
Brown, S.A. Recovery patterns in adolescent substance abuse. In: Baer, J.S.,
Marlatt, G.A. and McMahon, R.J. (Eds.) Addictive Behaviors Across the Life Span:
Prevention, Treatment, and Policy Issues, Thousand Oaks, CA: Sage, 1993, pp.
Brown, S.A., Tapert, S.F., Granholm, E. and Delis, D.C. Neurocognitive functioning
of adolescents: Effects of protracted alcohol use. Alcsm Clin. Exp. Res 24:
Brunell, S.C., Rajendran, P. and Spear, L.P. Ethanol intake and stress adaptation
in adolescent and adult rats. Soc. Neurosci. Abstr. 27: 877.12, 2001.
Choi, S. and Kellogg, C.K. Norepinephrine utilization in the hypothalamus of
the male rat during adolescent development. Devel. Neurosci. 14: 369-376,
Choi, S. and Kellogg, C.K. Adolescent development influences functional responsiveness
of noradrenergic projections to the hypothalamus in male rats. Devel. Brain
Res. 94: 144-151, 1996.
Choi, S., Weisberg, S.N. and Kellogg, C.K. Control of endogenous norepinephrine
release in the hypothalamus of male rats changes over adolescent development.
Devel. Brain Res. 98: 134-141, 1997.
Cicero, T.J., Adams, M.L., O'Connor, L., Nock, B., Meyer, E.R. and Wozniak,
D. Influence of chronic alcohol administration on representative indices of
puberty and sexual maturation in male rats and the development of their progeny.
J. Pharmacol. Exp. Therapeut. 255: 707-715, 1990.
Clark, D.B., Kirisci, L. and Tarter, R.E. Adolescent versus adult onset and
the development of substance use disorders in males. Drug Alcohol Depend. 49:
Coulter, C.L., Happe, H.K. and Murrin, L.C. Postnatal development of the dopamine
transporter: A quantitative autoradiographic study. Devel. Brain Res. 92:
Crews, F.T., Braun, C.J., Hoplight, B., Switzer, R.C., 3rd and Knapp, D.J.
Binge ethanol consumption causes differential brain damage in young adolescent
rats compared with adult rats. Alcsm Clin. Exp. Res. 24: 1712-1723, 2000.
Csikszentmihalyi, M., Larson, R. and Prescott, S. The ecology of adolescent
activity and experience. J. Youth Adolesc. 6: 281-294, 1977.
De Bellis, M.D., Clark, D.B., Beers, S.R., Soloff, P.H., Boring, A.M., Hall,
J., Kersh, A. and Keshavan, M.S. Hippocampal volume in adolescent-onset alcohol
use disorders. Amer. J. Psychiat. 157: 737-744, 2000.
Dees, W.L., Skelley, C.W., Hiney, J.K. and Johnston, C.A. Actions of ethanol
on hypothalamic and pituitary hormones in prepubertal female rats. Alcohol 7:
Deykin, E.Y., Levy, J.C. and Wells, V. Adolescent depression, alcohol and drug
abuse. Amer. J. Publ. Hlth 77: 178-182, 1987.
Diamond, A. Guidelines for the study of brain-behavior relationships during
development. In: Levin, H.S., Eisenberg, H.M. and Benton, A.L. (Eds.) Frontal
Lobe Function and Dysfunction, New York: Oxford Univ. Press, 1991, pp. 339-378.
Donovan, J.E. Young adult drinking-driving: Behavioral and psychosocial correlates.
J. Stud. Alcohol 54: 600-613, 1993.
Dubas, J.S. Cognitive abilities and physical maturation. In: Lerner, R.M., Petersen, A.C. and Brooks-Gunn, J. (Eds.) Encyclopedia
of Adolescence, Vol. 1, New York: Garland, 1991, pp. 133-138.
Dumas, T.C. and Foster, T.C. Late developmental changes in the ability of adenosine
A1 receptors to regulate synaptic transmission in the hippocampus. Devel. Brain
Res. 105: 137-139, 1998.
Dunn, A.J. and Kramarcy, N.R. Neurochemical responses in stress: Relationships
between the hypothalamic-pituitary-adrenal and catecholamine systems. In: Iversen,
L.L., Iversen, S.D. and Snyder, S.H. (Eds.) Handbook of Psychopharmacology,
Vol. 18, New York: Plenum, 1984, pp. 455-515.
Ernst, A.J., Dempster, J.P., Yee, R., St. Dennis, C. and Nakano, L. Alcohol
toxicity, blood alcohol concentration and body water in young and adult rats.
J. Stud. Alcohol 37: 347-356, 1976.
Fahlke, C., Engel, J.A., Eriksson, C.J., Hard, E. and Soderpalm, B. Involvement
of corticosterone in the modulation of ethanol consumption in the rat. Alcohol
11: 195-202, 1994.
Fassino, M.J. and Campbell, B.A. The ontogeny of play in rats. Paper presented
at the meeting of the Eastern Psychological Association, New York, 1981.
Fergusson, D.M., Lynskey, M.T. and Horwood, L.J. Childhood exposure to alcohol
and adolescent drinking patterns. Addiction 89: 1007-1016, 1994.
Ferris, C.F., Shtiegman, K. and King, J.A. Voluntary ethanol consumption in
male adolescent hamsters increases testosterone and aggression. Physiol. Behav.
63: 739-744, 1998.
Friedman, J. and Humphrey, J.A. Antecedents of collegiate drinking. J. Youth
Adolesc. 14: 11-21, 1985.
Gabriel, S.M., Roncancio, J.R. and Ruiz, N.S. Growth hormone pulsatility and
the endocrine milieu during sexual maturation in male and female rats. Neuroendocrinology
56: 619-625, 1992.
Galloway, M.P., Wolf, M.E. and Roth, R.H. Regulation of dopamine synthesis
in the medial prefrontal cortex is mediated by release modulating autoreceptors:
Studies in vivo. J. Pharmacol. Exp. Therapeut. 236: 689-698, 1986.
Ganji, V. and Betts, N. Fat, cholesterol, fiber and sodium intakes of US population:
Evaluation of diets reported in 1987-88 Nationwide Food Consumption Survey.
Europ. J. Clin. Nutr. 49: 915-920, 1995.
Gardner, E.L. The neurobiology and genetics of addiction: Implications of the
“reward deficiency syndrome” for therapeutic strategies in chemical
dependency. In: Elster, J. (Ed). Addiction: Entries and Exits, New York: Russell
Sage Foundation, 1999, pp. 57-119.
Gelbard, H.A., Teicher, M.H., Faedda, G. and Baldessarini, R.J. Postnatal development
of Dopamine D1 and D2 receptor sites in rat striatum. Devel. Brain
Res. 49: 123-130, 1989.
Goeders, N.E. A neuroendocrine role in cocaine reinforcement. Psychoneuroendocrinology
22: 237-259, 1997.
Goldman, L., Winget, C., Hollingshead, G.W. and Levine, S. Postweaning development
of negative feedback in the pituitary-adrenal system of the rat. Neuroendocrinology
12: 199-211, 1973.
Goodrick, C.L. Alcohol preference of the male Sprague-Dawley albino rat as
a function of age. J. Gerontol. 22: 369-371, 1967.
Gould, E., Woolf, N.J. and Butcher, L.L. Postnatal development of cholinergic
neurons in the rat: I. Forebrain. Brain Res. Bull. 27: 767-789, 1991.
Grant, B.F. and Dawson, D.A. Age at onset of alcohol use and its association
with DSM-IV alcohol abuse and dependence: Results from the National Longitudinal
Alcohol Epidemiologic Survey. J. Subst. Abuse 9: 103-110, 1997.
Hansell, S. and White, H.R. Adolescent drug use, psychological distress, and
physical symptoms. J. Hlth Social Behav. 32: 288-301, 1991.
Hawkins, J.D., Graham, J.W., Maguin, E., Abbott, R., Hill, K.G. and Catalano,
R.F. Exploring the effects of age of alcohol use initiation and psychosocial
risk factors on subsequent alcohol misuse. J. Stud. Alcohol 58: 280-290,
Hayashi, T. and Tadokoro, S. Learning retardation and enhanced ethanol preference
produced by postnatal pretreatments with ethanol in adult rats. Jap. J. Pharmacol.
37: 269-276, 1985.
Ho, A., Chin, A.J. and Dole, V.P. Early experience and the consumption of alcohol
by adult C57BL/6J Mice. Alcohol 6: 511-515, 1989.
Hollstedt, C., Olsson, O. and Rydberg, U. Effects of ethanol on the developing
rat: II. Coordination as measured by the tilting-plane test. Med. Biol. 58:
Hollstedt, C. and Rydberg, U. Postnatal effects of alcohol on the developing
rat. In: Rydberg, U., Alling, C. and Engel, J. (Eds.) Alcohol and the Developing
Brain, New York: Raven Press, 1985, pp. 69-84.
Huttenlocher, P.R. Synapse elimination and plasticity in developing human cerebral
cortex. Amer. J. Mental Defic. 88: 488-496, 1984.
Irwin, C.E., Jr. and Millstein, S.G. Correlates and predictors of risktaking
behavior during adolescence. In: Lipsitt, L.P. and Mitnick, L.L. (Eds.) Self-Regulatory
Behavior and Risk Taking: Causes and Consequences, Norwood, NJ: Ablex, 1992,
Jernigan, T.L., Trauner, D.A., Hesselink, J.R. and Tallal, P.A. Maturation
of human cerebrum observed in vivo during adolescence. Brain 114 (Pt
5): 2037-2049, 1991.
Johnston, L.D., O'Malley, P.M. and Bachman, J.G. National survey results on
Drug Use from the Monitoring the Future Study, 1975-2000, Vol. 1, NIH Publication
No. 01-4924, Bethesda, MD: Department of Health and Human Services, 2001.
Kakihana, R. and McClearn, G.E. Development of alcohol preference in BALB/c
mice. Nature 199: 511-512, 1963.
Kalsbeek, A., Voorn, P., Buijs, R.M., Pool, C.W. and Uylings, H.B. Development
of the dopaminergic innervation in the prefrontal cortex of the rat. J. Comp.
Neurol. 269: 58-72, 1988.
Keir, W.J. and Deitrich, R.A. Development of central nervous system sensitivity
to ethanol and pentobarbital in short- and long-sleep mice. J. Pharmacol. Exp.
Therapeut. 254: 831-835, 1990.
Kennedy, G.C. and Mitra, J. Body weight and food intake as initiating factors
for puberty in the rat. J. Physiol. 166: 408-418, 1963.
Kiess, W., Meidert, A., Dressendörfer, R.A., Schriever, K., Kessler, U.,
König, A., Schwarz, H.P. and Strasburger, C.J. Salivary cortisol levels
throughout childhood and adolescence: Relation with age, pubertal stage, and
weight. Pediat. Res. 37 (4 Pt 1): 502-506, 1995.
Kilpatrick, D.G., Acierno, R., Saunders, B., Resnick, H.S., Best, C.L. and
Schnurr, P.P. Risk factors for adolescent substance abuse and dependence: Data
from a national sample. J. Cons. Clin. Psychol. 68: 19-30, 2000.
Koob, G.F. Neural mechanisms of drug reinforcement. Ann. N.Y. Acad. Sci. 654:
Kostovic, I. Structural and histochemical reorganization of the human prefrontal
cortex during perinatal and postnatal life. In: Uylings, H.B.M., van Eden, C.G.,
De Bruin, J.P.C., Corner, M.A. and Feenstra, M.G.P. (Eds.) Progress in Brain
Research, Vol. 85: The Prefrontal Cortex: Its Structure, Function and Pathology,
New York: Elsevier Science, 1990, pp. 223-240.
Kurtz, M.M. and Campbell, B.A. Paradoxical autonomic responses to aversive
stimuli in the developing rat. Behav. Neurosci. 108: 962-971, 1994.
Labouvie, E., Bates, M.E. and Pandina, R.J. Age of first use: Its reliability
and predictive utility. J. Stud. Alcohol 58: 638-643, 1997.
Lancaster, F.E., Brown, T.D., Coker, K.L., Elliott, J.A. and Wren, S.B. Sex
differences in alcohol preference and drinking patterns emerge during the early
postpubertal period in Sprague-Dawley rats. Alcsm Clin. Exp. Res. 20:
Larson, R. and Asmussen, L. Anger, worry, and hurt in early adolescence: An
enlargin g world of negative emotions. In: Colten, M.E. and Gore, S. (Eds.)
Adolescent Stress: Causes and Consequences, Hawthorne, NY: Aldine de Gruyter,
1991, pp. 21-41.
Larson, R. and Richards, M.H. (Eds.) Divergent Realities: The Emotional Lives
of Mothers, Fathers, and Adolescents, New York: Basic Books, 1994.
Laurent, J., Catanzaro, S.J. and Callan, M.K. Stress, alcohol-related expectancies
and coping preferences: A replication with adolescents of the Cooper et al.
(1992) model. J. Stud. Alcohol 58: 644-651, 1997.
Lewis, D.A. Development of the prefrontal cortex during adolescence: Insights
into vulnerable neural circuits in schizophrenia. Neuropsychopharmacology 16:
Little, P.J., Kuhn, C.M., Wilson, W.A. and Swartzwelder, H.S. Differential
effects of ethanol in adolescent and adult rats. Alcsm Clin. Exp. Res. 20:
Maier, D.M. and Pohorecky, L.A. The effect of stress on tolerance to ethanol
in rats. Alcohol Drug Res. 6: 387-401, 1986.
Markwiese, B.J., Acheson, S.K., Levin, E.D., Wilson, W.A. and Swartzwelder,
H.S. Differential effects of ethanol on memory in adolescent and adult rats.
Alcsm Clin. Exp. Res. 22: 416-421, 1998.
Meaney, M.J., Sapolsky, R.M. and McEwen, B.S. The development of the glucocorticoid
receptor system in the rat limbic brain: I. Ontogeny and autoregulation. Brain
Res. 350 (1-2): 159-164, 1985a.
Meaney, M.J., Sapolsky, R.M. and McEwen, B.S. The development of the glucocorticoid
receptor system in the rat limbic brain: II. An autoradiographic study. Brain
Res. 350 (1-2): 165-168, 1985b.
Moy, S.S., Duncan, G.E., Knapp, D.J. and Breese, G.R. Sensitivity to ethanol
across development in rats: Comparison To [³H] zolpidem binding. Alcsm
Clin. Exp. Res. 22: 1485-1492, 1998.
Nance, D.M. The developmental and neural determinants of the effects of estrogen
on feeding behavior in the rat: A theoretical perspective. Neurosci. Biobehav.
Rev. 7: 189-211, 1983.
Odell, W.D. Sexual maturation in the rat. In: Grumbach, M.M., Sizonenko, P.C.
and Aubert, M.L. (Eds.) Control of the Onset of Puberty, Philadelphia, PA: Lippincott
Williams & Wilkins, 1990, pp. 183-210.
Ojeda, S.R. and Urbanski, H.F. Puberty in the rat. In: Knobil, E. and Neill,
J.D. (Eds.) The Physiology of Reproduction, 2nd Edition, New York: Raven Press,
1994, pp. 363-409.
Osborne, G.L. and Butler, A.C. Enduring effects of periadolescent alcohol exposure
on passive avoidance performance in rats. Physiol. Psychol. 11: 205-208,
Parisella, R.M. and Pritham, G.H. Effect of age on alcohol preference by rats.
Q. J. Stud. Alcohol 25: 248-252, 1964.
Petersen, A.C., Silbereisen, R.K. and Soerenson, S. Adolescent development:
A global perspective. In: Hurrelmann, K. and Hamilton, S.F. (Eds.) Social Problems
and Social Contexts in Adolescence: Perspectives Across Boundaries, Hawthorne,
NY: Aldine De Gruyter, 1996, pp. 3-37.
Piazza, P.V., Rougé-Pont, F., Deminière, J.M., Kharoubi, M.,
LeMoal, M. and Simon, H. Dopaminergic activity is reduced in the prefrontal
cortex and increased in the nucleus accumbens of rats predisposed to develop
amphetamine self-administration. Brain Res. 567: 169-174, 1991.
Pohorecky, L.A. Interaction of ethanol and stress: Research with experimental
animalsan update. Alcohol Alcsm 25 (2-3): 263-276, 1990.
Pohorecky, L.A. Stress and alcohol interaction: An update of human research.
Alcsm Clin. Exp. Res. 15: 438-459, 1991.
Pollock, N.K. and Martin, C.S. Diagnostic orphans: Adolescents with alcohol
symptoms who do not qualify for DSM-IV abuse or dependence diagnoses. Amer.
J. Psychiat. 156: 897-901, 1999.
Post, G.B. and Kemper, H.C. Nutrient intake and biological maturation during
adolescence. The Amsterdam Growth and Health Longitudinal Study. Europ. J. Clin.
Nutr. 47: 400-408, 1993.
Prescott, C.A. and Kendler, K.S. Age at first drink and risk for alcoholism:
A noncausal association. Alcsm Clin. Exp. Res. 23: 101-107, 1999.
Primus, R.J. and Kellogg, C.K. Pubertal-related changes influence the development
of environment-related social interaction in the male rat. Devel. Psychobiol.
22: 633-643, 1989.
Rachal, J.V., Guess, L.L., Hubbard, R.L. and Maisto, S.A. Alcohol misuse by
adolescents. Alcohol Hlth Res. World 6: 61-68, 1982.
Ramaley, J.A. and Olson, J. Adrenal function in rats given PMS before puberty:
Response to ether stress. Neuroendocrinology 14: 1-13, 1974.
Rivier, C. Effect of the age of the rat and the duration of the stimulus on
stress-induced ACTH secretion. In: Weiner, H., Florin, I., Murison, R. and Hellhammer,
D. (Eds.) Frontiers of Stress Research, Toronto, Canada: Hans Huber, 1989, pp.
Robins, L.N. and McEvoy, L. Conduct problems as predictors of substance abuse.
In: Robins, L.N. and Rutter, M. (Eds.) Straight and Devious Pathways from Childhood
to Adulthood, New York: Cambridge Univ. Press, 1990, pp. 182-204.
Robins, L.N. and Przybeck, T.R. Age of onset of drug use as a factor in drug
and other disorders. In: Jones, C.L. and Battjes, R.J. (Eds.) Etiology of Drug
Abuse: Implications for Prevention. NIDA Research Monograph No. 56, DHHS Publication
No. (ADM) 85-1335, Washington: Government Printing Office, 1985, pp. 178-192.
Rosenberg, D.R. and Lewis, D.A. Changes in the dopaminergic innervation of
monkey prefrontal cortex during late postnatal development: A tyrosine hydroxylase
immunohistochemical study. Biol. Psychiat. 36: 272-277, 1994.
Sapolsky, R.M., Meaney, M.J. and McEwen, B.S. The development of the glucocorticoid
receptor system in the rat limbic brain: III. Negative-feedback regulation.
Brain Res. 350 (1-2): 169-173, 1985.
Scharf, A.A. Environmental stress, potential protective factors, and adolescent
risk-taking. Dissert. Abstr. Int. 59 (8-B): 4513, 1999.
Scheier, L.M., Botvin, G.J. and Miller, N.L. Life events, neighborhood stress,
psychosocial functioning, and alcohol use among urban minority youth. J. Child
Adolesc. Subst. Abuse 9: 19-50, 1999.
Schlegel, A. and Barry, H., 3rd (Eds.) Adolescence: An Anthropological Inquiry,
New York: Free Press, 1991.
Seeman, P., Bzowej, N.H., Guan, H.-C., Bergeron, C., Becker, L.E., Reynolds,
G.P., Bird, E.D., Riederer, P., Jellinger, K., Watanabe, S. and Tourtellotte,
W.W. Human brain dopamine receptors in children and aging adults. Synapse 1:
Shtiegman, K., King, J.A. and Ferris, C.F. Voluntary ethanol consumption during
adolescence in golden hamsters elevates blood testosterone and increases aggression
in early adulthood. Poster presented at the meeting of the Society for Neuroscience,
New Orleans, LA, 1997.
Silveri, M.M. and Spear, L.P. Decreased sensitivity to the hypnotic effects
of ethanol early in ontogeny. Alcsm Clin. Exp. Res. 22: 670- 676, 1998.
Silveri, M.M. and Spear, L.P. Ontogeny of rapid tolerance to the hypnotic effects
of ethanol. Alcsm Clin. Exp. Res. 23: 1180-1184, 1999.
Silveri, M.M. and Spear, L.P. Ontogeny of ethanol elimination and ethanol-induced
hypothermia. Alcohol 20: 45-53, 2000.
Silveri, M.M. and Spear, L.P. Acute, rapid, and chronic tolerance during ontogeny:
Observations when equating ethanol perturbation across age. Alcsm Clin. Exp.
Res. 25: 1301-1308, 2001.
Silveri, M.M. and Spear, L.P. The effects of NMDA and GABAA pharmacological
manipulations of ethanol sensitivity in immature and mature animals. Alcsm Clin.
Exp. Res., in press.
Slawecki, C.J., Betancourt, M., Cole, M. and Ehlers, C.L. Periadolescent alcohol
exposure has lasting effects on adult neurophysiological function in rats. Devel.
Brain Res. 128: 63-72, 2001.
Spear, L.P. The adolescent brain and age-related behavioral manifestations.
Neurosci. Biobehav. Rev. 24: 417-463, 2000.
Spear, L.P. and Brake, S.C. Periadolescence: Age-dependent behavior and psychopharmacological
responsivity in rats. Devel. Psychobiol. 16: 83-109, 1983.
Spear, L.P., Shalaby, I.A. and Brick, J. Chronic administration of haloperidol
during development: Behavioral and psychopharmacological effects. Psychopharmacology
70: 47-58, 1980.
Spiers, D.E. and Fusco, L.E. Age-dependent differences in the thermoregulatory
response of the immature rat to ethanol. Alcsm Clin. Exp. Res. 15: 23-28,
Stanwood, G.D., McElligot, S., Lu, L. and McGonigle, P. Ontogeny of dopamine
D3 receptors in the nucleus accumbens of the rat. Neurosci. Lett. 223:
Stone, E.A. and Quartermain, D. Greater behavioral effects of stress in immature
as compared to mature male mice. Physiol. Behav. 63: 143-145, 1997.
Susman, E.J., Inoff-Germain, G., Nottelmann, E.D., Loriaux, D.L., Cutler, G.B.,
Jr. and Chrousos, G.P. Hormones, emotional disposition, and aggressive attributes
in young adolescents. Child Devel. 58: 1114-1134, 1987.
Sussman, S. and Dent, C.W. One-year prospective prediction of drug use from
stress-related variables. Subst. Use Misuse 35: 717-735, 2000.
Swartzwelder, H.S., Richardson, R.C., Markwiese-Foerch, B., Wilson, W.A. and
Little, P.J. Developmental differences in the acquisition of tolerance to ethanol.
Alcohol 15: 311-314, 1998.
Swartzwelder, H.S., Wilson, W.A. and Tayyeb, M.I. Differential sensitivity
of NMDA receptor-mediated synaptic potentials to ethanol in immature versus
mature hippocampus. Alcsm Clin. Exp. Res. 19: 320- 323, 1995a.
Swartzwelder, H.S., Wilson, W.A. and Tayyeb, M.I. Age-dependent inhibition
of long-term potentiation by ethanol in immature versus mature hippocampus.
Alcsm Clin. Exp. Res. 19: 1480-1485, 1995b.
Teicher, M.H., Andersen, S.L. and Hostetter, J.C., Jr. Evidence for dopamine
receptor pruning between adolescence and adulthood in striatum but not nucleus
accumbens. Devel. Brain Res. 89: 167-172, 1995.
Teicher, M.H., Barber, N.I., Gelbard, H.A., Gallitano, A.L., Campbell, A.,
Marsh, E. and Baldessarini, R.J. Developmental differences in acute nigrostriatal
and mesocorticolimbic system response to haloperidol. Neuropsychopharmacology
9: 147-156, 1993.
Teicher, M.H., Gallitano, A.L., Gelbard, H.A., Evans, H.K., Marsh, E.R., Booth,
R.G. and Baldessarini, R.J. Dopamine D1 autoreceptor function: Possible expression
in developing rat prefrontal cortex and striatum. Devel. Brain Res. 63
(1-2): 229-235, 1991.
Tolliver, G.A. and Samson, H.H. The influence of early postweaning ethanol
exposure on oral self-administration behavior in the rat. Pharmacol. Biochem.
Behav. 38: 575-580, 1991.
Tschann, J.M., Adler, N.E., Irwin, C.E., Jr., Millstein, S.G., Turner, R.A.
and Kegeles, S.M. Initiation of substance use in early adolescence: The roles
of pubertal timing and emotional distress. Hlth Psychol. 13: 326-333,
Unger, J.B., Li, Y., Johnson, C.A., Gong, J., Chen, X., Li, C.Y., Trinidad,
D.R., Tran, N.T. and Lo, A.T. Stress life events among adolescents in Wuhan,
China: Associations with smoking, alcohol use, and depressive symptoms. Int.
J. Behav. Med. 8: 1-18, 2001.
van Eden, C.G., Kros, J.M. and Uylings, H.B.M. The development of the rat prefrontal
cortex: Its size and development of connections with thalamus, spinal cord and
other cortical areas. In: Uylings, H.B.M., van Eden, C.G., De Bruin, J.P.C.,
Corner, M.A. and Feenstra, M.G.P. (Eds.) Progress in Brain Research: Vol. 85.
The Prefrontal Cortex: Its Structure, Function and Pathology, New York: Elsevier
Science, 1990, pp. 169-183.
Varlinskaya, E.I. and Spear, L.P. Anxiolytic effects of ethanol in adolescent
and adult rats. Poster presented at the meeting of the Research Society on Alcoholism,
Montreal, Canada, 2001.
Wagner, E.F. Delay of gratification, coping with stress, and substance use
in adolescence. Exp. Clin. Psychopharmacol. 1 (1-4): 27-43, 1993.
Walker, C.-D., Perrin, M., Vale, W. and Rivier, C. Ontogeny of the stress response
in the rat: Role of the pituitary and the hypothalamus. Endocrinology 118:
Walker, C.-D., Trottier, G., Rochford, J. and Lavallée, D. Dissociation
between behavioral and hormonal responses to the forced swim stress in lactating
rats. J. Neuroendocrinol. 7: 615-622, 1995.
Walker, E.F. and Diforio, D. Schizophrenia: A neural diathesis-stress model.
Psychol. Rev. 104: 667-685, 1997.
Whalen, C.K., Jamner, L.D., Henker, B. and Delfino, R.J. Smoking and moods
in adolescents with depressive and aggressive dispositions: Evidence from surveys
and electronic diaries. Hlth Psychol. 20: 99-111, 2001.
White, A.M., Ghia, A.J., Levin, E.D. and Swartzwelder, H.S. Binge pattern ethanol
exposure in adolescent and adult rats: Differential impact on subsequent responsiveness
to ethanol. Alcsm Clin. Exp. Res. 24: 1251-1256, 2000.
Wills, T.A. Stress and coping in early adolescence: Relationships to substance
use in urban school samples. Hlth Psychol. 5: 503-529, 1986.
Wolfer, D.P. and Lipp, H.-P. Evidence for physiological growth of hippocampal
mossy fiber collaterals in the guinea pig during puberty and adulthood. Hippocampus
5: 329-340, 1995.
Yamaguchi, K. and Kandel, D.B. Patterns of drug use from adolescence to young
adulthood: III. Predictors of progression. Amer. J. Publ. Hlth 74: 673-681,
York, J.L. and Chan, A.W. Age-related differences in sensitivity to alcohol
in the rat. Alcsm Clin. Exp. Res. 17: 864-869, 1993.
Zecevic, N., Bourgeois, J.-P. and Rakic, P. Changes in synaptic density in
motor cortex of rhesus monkey during fetal and postnatal life. Devel. Brain
Res. 50: 11-32, 1989.
Zorzano, A. and Herrera, E. Decreased in vivo rate of ethanol metabolism in
the suckling rat. Alcsm Clin. Exp. Res. 13: 527-532, 1989.
*Preparation of this article was supported in part
by National Institute on Alcohol Abuse and Alcoholism grants R37 AA12525 and
Last reviewed: 9/23/2005