Effects Of Adolescent Ethanol Exposure Research Articles

Effects of Adolescent Ethanol Exposure on Taste Sensitivity and Preference in Male and Female Mice

Adolescent alcohol use is prevalent in the U.S. and there is increasing evidence that neural and behavioral consequences of adolescent alcohol use may differentially alter the developing neural circuitry in males and females. Taste has been implicated in the preference for and intake of alcohol and alcohol exposure regulates taste perception. Data from our laboratory indicate that adolescent ethanol exposure (AIE) significantly alters lingual expression of fat and sweet taste receptors and decreases the density of fungiform papillae in male and female mice. The goal of the current study was to examine the effects of adolescent ethanol exposure (AIE) on the taste preference thresholds for fat and sweet tastants in male and female C57/Bl6 mice. Mice (postnatal day (P)27) were exposed to intermittent ethanol vapor or volatilized water. The AIE protocol was run for two, 4-day cycles of 16h in-chamber sessions and 8h out-of-chamber sessions separated by 3 days from P27-P35. Ethanol vapor chambers were maintained to achieve blood alcohol concentrations ~ 200mg/dL. One week following the last ethanol exposure, mice (n=9-10/group) were given access to two bottles, one containing a control solution and one containing increasing concentrations of either sucrose or linoleic acid. A single concentration of sucrose was presented to each mouse for 48 hours [0.1, 0.25, 0.5, 1.0, 2.0, 4.0%]. Following access to all concentrations of sucrose, a single concentration of linoleic acid (in 0.3% Xanthan gum) was presented to each mouse for 48 hours [0.0025, 0.025, 0.25, 0.5, 1.0, 2.0%]. Following access to linoleic acid, each mouse received a solution of 1.0% sucrose plus 0.25% linoleic acid for 24 hours. Total intake of the tastant was determined and the preference for each concentration was calculated. A percent intake of 50% is indicative of no preference between solutions. Mice preferred the sucrose solution to the control solution at all concentrations tested. Males had a higher preference for 0.25% sucrose than females and significant effects of AIE and sex were detected at 2.0% sucrose, with males demonstrating a higher preference for sucrose and mice exposed to AIE exhibiting a higher preference for the sucrose solution. No preference or aversion for lower concentrations of linoleic acid were detected (0.0025-0.25%) in females, however, AIE significantly decreased linoleic acid preference (0.5%, 1.0%, 2.0%) compared to air-exposed females. Linoleic acid preference at concentrations of 0.5% and 1.0% was significantly lower than the preference for the control solution and was considered aversive in females. Males were able to detect linoleic acid at lower concentrations than females, and males exposed to AIE exhibited a higher preference for 0.025% linoleic acid, compared to air-exposed males. Linoleic acid at concentrations of 0.025, 0.25 and 2.0% were significantly lower than the preference for the control solution and were considered aversive in males. In males exposed to AIE, the 1.0% sucrose/0.25% linoleic acid solution was preferred over the control solution. These data support our previous findings that ethanol exposure, using this model, significantly alters taste receptor mRNA expression on the circumvallate papillae and fungiform papillae density in adolescent male and female mice. Further understanding of ethanol’s effect on taste sensitivity is needed to better understand the long-term effects of adolescent ethanol exposure on food and beverage preferences and consumption patterns. NIH AA028011 T.W. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of adolescent ethanol exposure on adult nondrug reward seeking behavior in male and female mice.

Adolescent alcohol use is associated with an increased likelihood of developing an alcohol use disorder in adulthood, potentially due to the effects of alcohol exposure on reward-seeking behavior. However, it remains unclear whether adolescent drinking is sufficient to alter nondrug reward seeking in adulthood. As adolescence is a period of both brain and sexual maturation, which occur in a sex-dependent manner, males and females may be differentially sensitive to the consequences of adolescent alcohol exposure. The present study investigated whether adolescent ethanol exposure affected food reward taking and seeking in male and female adult mice. Male and female C57BL/6J mice underwent intermittent ethanol exposure (AIE) via vapor inhalation during early adolescence (28-42 days of age). At 10 weeks of age, the mice were trained in a conditioned place preference paradigm (CPP) for a food reward. We measured food consumption, CPP, and cFos expression in multiple brain regions following CPP testing. Data were analyzed using repeated measures analysis of variance with exposure (air vs. AIE), sex, and time as factors. AIE exposure increased food consumption during CPP training in adult male mice, but reduced pellet consumption in adult female mice. AIE exposure impaired CPP expression only in female mice. Despite these behavioral differences, exposure to the reward-paired chamber did not induce differential cFos expression following CPP testing in the prelimbic and infralimbic cortices or the nucleus accumbens core and shell. These findings indicate that adolescent ethanol exposure disrupted nondrug reward taking and seeking in adulthood in female mice and altered consumption in adult male mice.

Use of a Fitbit-like device in rats: Sex differences, relation to EEG sleep, and use to measure the long-term effects of adolescent ethanol exposure.

Sleep difficulties and rhythm disturbances are some of the problems associated with adolescent binge drinking. Recently, animal models of alcohol-induced insomnia have been developed. However, studies in human subjects have recently focused not only on nighttime EEG findings but also on daytime sleepiness and disrupted activity levels as typically measured by activity tracking devices such as the "Fitbit." We sought to develop and test a Fitbit-like device (the "FitBite") in rats and use it to track rest-activity cycles following adolescent alcohol exposure. The effects of 5 weeks of adolescent ethanol vapor or control conditions were evaluated in 48 male and female Wistar rats using FitBite activity while intoxicated, and during acute (24 h post-vapor exposure) and chronic withdrawal (4 weeks post-vapor exposure). Data were analyzed using activity count and cosinor analyses. Fourteen rats were subsequently implanted with cortical electrodes, and data from the FitBite were compared with EEG data to determine how well the FitBite could identify sleep and activity cycles. Female rats were generally more active than males, with higher circadian rhythm amplitudes and mesors (rhythm-adjusted means) across a 24-h period. There were significant correlations between EEG-estimated sleep and activity counts using the FitBite. When the rats were tested during intoxication after 4 weeks of ethanol vapor exposure, they had significantly less overall activity. Disruptions in circadian rhythm were also found with significant decreases in the circadian amplitude, mesor, and a later shift in the acrophase. At 24 h of ethanol withdrawal, rats had more episodes of activity with shorter durations during the daytime, when rats are expected to spend more of their time sleeping. This effect remained at 4 weeks following withdrawal, but circadian rhythm disruptions were no longer present. A Fitbit-like device can be successfully used in rats to assess rest-activity cycles. Adolescent alcohol exposure produced circadian rhythm disturbances that were not observed after withdrawal. Fragmentation of ultradian rest-activity cycles during the light period was found at 24 h and 4 weeks after withdrawal and support data demonstrating the presence of sleep disturbance long after alcohol withdrawal.

Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions.

Adolescence is a developmental period that encompasses, but is not limited to, puberty and continues into early adulthood. During this period, maturation and refinement are observed across brain regions such as the prefrontal cortex (PFC), which is critical for cognitive function. Adolescence is also a time when excessive alcohol consumption in the form of binge drinking peaks, increasing the risk of long-term cognitive deficits and the risk of developing an alcohol use disorder later in life. Animal models have revealed that adolescent ethanol (EtOH) exposure results in protracted disruption of neuronal function and performance on PFC-dependent tasks that require higher-order decision-making. However, the role of astrocytes in EtOH-induced disruption of prefrontal cortex-dependent function has yet to be elucidated. Astrocytes have complex morphologies with an extensive network of peripheral astrocyte processes (PAPs) that ensheathe pre- and postsynaptic terminals to form the ‘tripartite synapse.’ At the tripartite synapse, astrocytes play several critical roles, including synaptic maintenance, dendritic spine maturation, and neurotransmitter clearance through proximity-dependent interactions. Here, we investigate the effects of adolescent binge EtOH exposure on astrocyte morphology, PAP-synaptic proximity, synaptic stabilization proteins, and dendritic spine morphology in subregions of the PFC that are important in the emergence of higher cognitive function. We found that adolescent binge EtOH exposure resulted in subregion specific changes in astrocyte morphology and astrocyte-neuronal interactions. While this did not correspond to a loss of astrocytes, synapses, or dendritic spines, there was a corresponding region-specific and EtOH-dependent shift in dendritic spine phenotype. Lastly, we found that changes in astrocyte-neuronal interactions were not a consequence of changes in the expression of key synaptic structural proteins neurexin, neuroligin 1, or neuroligin 3. These data demonstrate that adolescent EtOH exposure results in enduring effects on neuron-glia interactions that persist into adulthood in a subregion-specific PFC manner, suggesting selective vulnerability. Further work is necessary to understand the functional and behavioral implications.

Long-lasting microbial dysbiosis and altered enteric neurotransmitters in adult rats following adolescent binge ethanol exposure.

Human alcoholism and ethanol exposure of adult mice cause acute microbial dysbiosis. Adolescent binge drinking is common, but the effect of adolescent ethanol exposure on the adult microbiome and enteric neurotransmitters has not been studied. In the current study, male Wistar rats received adolescent intermittent ethanol (AIE) treatment, and fecal samples were collected on postnatal day (P)54 and P95 for bacterial 16S rRNA amplicon sequencing. Cecal tissue was collected on P95 for analysis of innate immune and neurotransmitter marker expression. At the genus level, AIE treatment altered the relative abundance of several microbes, including decreased relative abundance of Dehalobacterium and CF231 (a member of the Paraprevotellaceae family) that persisted into adulthood. Across aging, the relative abundance of several microbes was altered in both control- and AIE-treated rats. At P95, AIE exposure was associated with increased cecal serotonin levels and reduced choline acetyltransferase gene expression. Taxonomic shifts at P54 and at P95 suggest that AIE causes both immediate and lasting microbial dysbiosis. The lasting microbial dysbiosis was accompanied by alterations of enteric neurotransmitters.

Episodic Ethanol Exposure in Adolescent Rats Causes Residual Alterations in Endogenous Opioid Peptides.

Adolescent binge drinking is associated with an increased risk of substance use disorder, but how ethanol affects the central levels of endogenous opioid peptides is still not thoroughly investigated. The aim of this study was to examine the effect of repeated episodic ethanol exposure during adolescence on the tissue levels of three different endogenous opioid peptides in rats. Outbred Wistar rats received orogastric (i.e., gavage) ethanol for three consecutive days per week between 4 and 9 weeks of age. At 2 h and 3 weeks, respectively, after the last exposure, beta-endorphin, dynorphin B and Met-enkephalin-Arg6Phe7 (MEAP) were analyzed with radioimmunoassay. Beta-endorphin levels were low in the nucleus accumbens during ethanol intoxication. Remaining effects of adolescent ethanol exposure were found especially for MEAP, with low levels in the amygdala, and high in the substantia nigra and ventral tegmental area three weeks after the last exposure. In the hypothalamus and pituitary, the effects of ethanol on beta-endorphin were dependent on time from the last exposure. An interaction effect was also found in the accumbal levels of MEAP and nigral dynorphin B. These results demonstrate that repeated episodic exposure to ethanol during adolescence affected opioid peptide levels in regions involved in reward and reinforcement as well as stress response. These alterations in opioid networks after adolescent ethanol exposure could explain, in part, the increased risk for high ethanol consumption later in life.

Under the influence: Effects of adolescent ethanol exposure and anxiety on motivation for uncertain gambling-like cues in male and female rats

Gambling disorder (GD) frequently co-occurs with alcohol use and anxiety disorders, suggesting possible shared mechanisms. Recent research suggests reward uncertainty may powerfully enhance attraction towards reward cues. Here, we examined the effects of adolescent ethanol exposure, anxiety, and reward uncertainty on cue-triggered motivation. Male and female adolescent rats were given free access to ethanol or control jello for 20days. Following withdrawal, rats underwent autoshaping on a certain (100%-1) or uncertain (50%-1-2-3) reward contingency, followed by single-session conditioned reinforcement and progressive ratio tasks, and 7days of omission training, during which lever pressing resulted in omission of reward. Finally, anxiety levels were quantified on the elevated plus maze. Here, we found that uncertainty narrowed cue attraction by significantly increasing the ratio of sign-tracking to goal-tracking, particularly amongst control jello and high anxiety animals, but not in animals exposed to ethanol during adolescence. In addition, attentional bias towards the lever cue was more persistent under uncertain conditions following omission training. We also found that females consumed more ethanol, and that uncertainty mitigated the anxiolytic effects of ethanol exposure observed in high ethanol intake animals under certainty conditions. Our results further support that reward uncertainty biases attraction towards reward cues, suggesting also that heightened anxiety may enhance vulnerability to the effects of reward uncertainty. Chronic, elevated alcohol consumption may contribute to heightened anxiety levels, while high anxiety may promote the over-attribution of incentive value to reward cues, highlighting possible mechanisms that may drive concurrent anxiety, heavy drinking, and problematic gambling.

Behavioral Inefficiency on a Risky Decision-Making Task in Adulthood after Adolescent Intermittent Ethanol Exposure in Rats

Adolescence is a period of development in neural circuits that are critical for adult functioning. There is a relationship between alcohol exposure and risky decision-making, though the enduring effects of adolescent ethanol exposure on risky decision-making in adulthood have not been fully explored. Studies using positive reinforcement have shown that adolescent intermittent ethanol (AIE) exposure results in higher levels of risky decision-making in adulthood, but the effects of AIE on punishment-mediated decision-making have not been explored. Adolescent rats were exposed to AIE or saline vehicle across a 16-day period, and then allowed to mature into adulthood. They were then trained to lever press for food reward and were assessed for risky decision-making by pairing increased levels of food reward with the probability of footshock punishment. AIE did not alter punishment-mediated risky decision-making. However, it did result in a significant increase in the delay to lever pressing. This finding is consistent with previous reports, using other behavioral tasks, which show decreased behavioral efficiency in adulthood after AIE. These findings indicate that AIE increases behavioral inefficiency, but not punishment-mediated risk-taking, in adulthood. Thus they contribute to a more nuanced understanding of the long-term effects of AIE on adult behavior.

Persistent Loss of Hippocampal Neurogenesis and Increased Cell Death following Adolescent, but Not Adult, Chronic Ethanol Exposure

Although adolescence is a common age to initiate alcohol consumption, the long-term consequences of exposure to alcohol at this time of considerable brain maturation are largely unknown. In studies utilizing rodents, behavioral evidence is beginning to emerge suggesting that the hippocampus may be persistently affected by repeated ethanol exposure during adolescence, but not by comparable alcohol exposure in adulthood. The purpose of this series of experiments was to explore a potential mechanism of hippocampal dysfunction in adults exposed to ethanol during adolescence. Given that disruption in adult neurogenesis has been reported to impair performance on tasks thought to be hippocampally related, we used immunohistochemistry to assess levels of doublecortin (DCX), an endogenous marker of immature neurons, in the dentate gyrus (DG) of the hippocampus 3-4 weeks after adolescent (postnatal day, PD28-48) or adult (PD70-90) intermittent ethanol exposure to 4 g/kg ethanol administered intragastrically. We also investigated another neurogenic niche, the subventricular zone (SVZ), to determine if the effects of ethanol exposure were region specific. Levels of cell proliferation and cell death were also examined in the DG via assessing Ki67 and cleaved caspase-3 immunoreactivity, respectively. Significantly less DCX was observed in the DG of adolescent (but not adult) ethanol-exposed animals about 4 weeks after exposure when these animals were compared to control age-mates. The effects of adolescent ethanol on DCX immunoreactivity were specific to the hippocampus, with no significant exposure effects emerging in the SVZ. In both the DG and the SVZ there was a significant age-related decline in neurogenesis as indexed by DCX. The persistent effect of adolescent ethanol exposure on reduced DCX in the DG appears to be related to significant increases in cell death, with significantly more cleaved caspase-3-positive immunoreactivity observed in the adolescent ethanol group compared to controls, but no alterations in cell proliferation when indexed by Ki67. These results suggest that a history of adolescent ethanol exposure results in lowered levels of differentiating neurons, probably due at least in part to increased cell death of immature neurons. These effects were evident in adulthood, weeks following termination of the chronic exposure, and may contribute to previously reported behavioral deficits on hippocampal-related tasks after chronic ethanol exposure in adolescence.

Peri-Adolescent Ethanol Vapor Exposure Produces Reductions in Hippocampal Volume that are Correlated with Deficits in Prepulse Inhibition of the Startle

Epidemiological studies suggest that excessive alcohol consumption is prevalent among adolescents and may have lasting neurobehavioral consequences. The use of animal models allows for the separation of the effects of adolescent ethanol (EtOH) exposure from genetic background and other environmental insults. In this study, the effects of moderate EtOH vapor exposure, during adolescence, on structural diffusion tensor imaging (DTI) and behavioral measures were evaluated in adulthood. A total of 53 Wistar rats were received at postnatal day (PD) 21 and were randomly assigned to EtOH vapor (14 hours on/10 hours off/day) or air exposure for 35 days from PD 23 to 58 (average blood ethanol concentration: 169 mg%). Animals were received in 2 groups that were subsequently sacrificed at 2 time points following withdrawal from EtOH vapor: (i) at 72 days of age, 2 weeks following withdrawal or (ii) at day 128, 10 weeks following withdrawal. In the second group, behavior in the light/dark box and prepulse inhibition (PPI) of the startle was also evaluated. Fifteen animals in each group were scanned, postmortem, for structural DTI. There were no significant differences in body weight between EtOH and control animals. Volumetric data demonstrated that total brain, hippocampal, corpus callosum but not ventricular volume were significantly larger in the 128-day-sacrificed animals as compared to the 72 day animals. The hippocampus was smaller and the ventricles larger at 128 days as compared to 72 days, in the EtOH-exposed animals, leading to a significant group × time effect. EtOH-exposed animals sacrificed at 128 days also had diminished PPI, and more rears in the light box were significantly correlated with hippocampal size. These studies demonstrate that DTI volumetric measures of hippocampus are significantly impacted by age and peri-adolescent EtOH exposure and withdrawal in Wistar rats.

Effects of adolescent ethanol exposure on event-related oscillations (EROs) in the hippocampus of adult rats

Electrophysiological studies have shown that adolescent ethanol (EtOH) exposure can produce long-term changes in hippocampal EEG and ERP activity. Recently, evidence has emerged suggesting that event-related oscillations (EROs) may be good indices of alcoholism risk in humans, however, have not been evaluated for their ability to index the effects of EtOH exposure. The objective of the present study was to characterize EROs generated in hippocampus in adult rats exposed to EtOH during adolescence. Adolescent male Sprague–Dawley rats were exposed to EtOH vapor for 12 h/d for 10 days. A time–frequency representation method was used to determine delta, theta, alpha and beta ERO energy and the degree of phase variation in the hippocampus of adult rats exposed to EtOH and age-matched controls. The present results suggest that the decrease in P3 amplitudes, previously observed in adult rats exposed to EtOH during adolescence, is associated with increases in evoked theta ERO energy. These studies suggest that EROs are suitable for characterizing the long-term effects of adolescent EtOH exposure. Further studies are needed to determine the relationship between the mechanisms that regulate these neurophysiological endophenotypes and the consequences of adolescent EtOH exposure.

Effects of adolescent ethanol exposure on Purkinje cell viability

Chronic alcoholism can cause damage to the cerebellum, an area of the brain associated with motor learning and coordination. Recently, we found that adolescent exposure to ethanol in rats can cause altered motor function in adulthood. In the current study, we investigated the effects of adolescent ethanol exposure on the viability of cerebellar Purkinje cells (PCs). To simulate binge drinking, male Sprague‐Dawley rats received an intraperitoneal (i.p.) injection of 25% (v/v) ethanol in isotonic saline (3g/kg) for either 7 days (P31‐37) or 4 days (P31,33,35,37). Controls received an i.p. injection of isotonic saline (P31‐37). Animals administered ethanol displayed obvious loss of motor coordination within minutes of injection. Blood alcohol concentration at 30 min was 275± 16 mg/dl, which represents approximately 12‐15 drink equivalents. On P58, rats were sacrificed and coronal slices of the cerebellum were prepared and stained with cresyl violet. Slices from control animals displayed an intact PC layer. However, rats that had received either 4 or 7 injections of ethanol had a significant loss of PCs as compared to controls. Given the importance of PCs in motor control, these findings suggest that PC death caused by adolescent ethanol exposure may lead to long‐lasting adverse effects on motor coordination. Supported by ABMRF/The Foundation for Alcohol Research and Canada Foundation for Innovation.

Adolescent ethanol experience alters immediate and long-term behavioral responses to ethanol odor in observer and demonstrator rats

BackgroundThe social transmission of food preference paradigm centers on the finding that observers obtain dietary information through olfactory cues on the breath of a demonstrator peer that has ingested a novel substance. This phenomenon plays a role in ethanol acceptability. Historically, studies using this technique have focused on observer animals in order to study the social transmission process. With respect to ethanol, studies of acute intoxication have shown that the pharmacologic properties of ethanol and hematogenic olfaction can influence the subsequent ethanol odor-mediated responses of the intoxicated animals. These acute studies, however, demonstrate odor aversion. The present study compared the effect of adolescent ethanol exposure, via the social transmission paradigm, on the behavioral response to ethanol odor in both observer and demonstrator animals in adolescence (postnatal day (P) 37) and the persistence of these effects into adulthood (P90).MethodsBeginning on P29, naïve rats received four ethanol or water exposures: one every 48 hours through either direct intragastric infusion or social interaction with an infused peer. The reflexive sniffing response of observers and demonstrators to ethanol odor was tested at P37 or P90 using whole-body plethysmography.ResultsThe behavioral response of adolescent ethanol observers and demonstrators significantly differed between themselves and from their respective water controls. Ethanol and water observers both displayed a greater response to ethanol odor than their respective demonstrator counterparts. Compared to controls, both modes of ethanol exposure produced similar magnitudes of enhancement. At P90, both forms of exposure displayed similar responses to ethanol odor and similar magnitudes of enhancement. Only demonstrators displayed equivalent enhanced responses in both sexes.ConclusionIn contrast to previous studies showing odor aversion following acute ethanol intoxication, within the context of the social transmission paradigm, adolescent demonstrators like observers showed an enhanced behavioral response to ethanol odor. The differential enhanced odor response between observers and demonstrators, despite similar net enhancements relative to controls, suggests the presence of a stress effect from the infusion technique. This finding contrasts previous suggestions that intragastric infusions create minimal stress: an important consideration when conducting ethanol research. This stress effect appears to ameliorate by adulthood.

Effects of adolescent ethanol exposure on sleep in adult rats

Although adolescent ethanol (EtOH) exposure has been associated with long-lasting changes in brain function, little is known as to whether EtOH exposure during adolescence alters sleep and cortical arousal. This study examined protracted alterations in sleep in adult rats exposed to EtOH during adolescence. Adolescent male Wistar rats were exposed to EtOH vapor for 12 h/day for 5 weeks. Cortical electroencephalograms were obtained during 4-h recording sessions after 5 weeks of withdrawal from EtOH. Adolescent EtOH exposure significantly reduced the mean duration of slow-wave sleep (SWS) episodes and the total amount of time spent in SWS in EtOH-exposed rats, compared to controls. Spectral analysis revealed that adolescent EtOH exposure significantly increased cortical peak frequencies during SWS in the 2–4, 4–6, and 6–8 Hz bands. Taken together, our findings suggest that chronic EtOH exposure in adolescent rats reduces measures of SWS, an effect also seen as part of normal aging. Although the cellular and molecular mechanisms mediating the consequences of EtOH exposure on the aging process are not known, the similarities between adolescent EtOH exposure and aging merits further investigation.

Adolescent Vulnerabilities to Chronic Alcohol or Nicotine Exposure: Findings From Rodent Models

This article presents an overview of the proceedings from a symposium entitled "Is adolescence special? Possible age-related vulnerabilities to chronic alcohol or nicotine exposure," organized by Susan Barron and Linda Spear and held at the 2004 Research Society on Alcoholism Meeting in Vancouver, British Columbia. This symposium, co-sponsored by the Fetal Alcohol Syndrome Study Group and the Neurobehavioral Teratology Society, focused on our current knowledge regarding the long-term consequences of ethanol and/or nicotine exposure during adolescence with the emphasis on data from rodent models. The support from these two societies represents the understanding by these research groups that adolescence represents a unique developmental stage for the effects of chronic drug exposure and also marks an age in which many risky behaviors including alcohol consumption and smoking typically begin. The speakers included (1) Aaron White, who presented data on the effects of adolescent ethanol exposure on subsequent motor or cognitive response to an ethanol challenge in adulthood; (2) Richard Bell, who presented data suggesting that genetic differences could play a role in adolescent vulnerability to ethanol; (3) Craig Slawecki, who presented data looking at the effects of chronic exposure to alcohol or nicotine on neurophysiologic and behavioral end points; and (4) Ed Levin, who presented data on acute and long-term consequences of adolescent nicotine exposure. Finally, Linda Spear provided some summary points and recommendations regarding unresolved issues and future directions.

Intermittent Ethanol Exposure in Adolescent Rats: Dose‐Dependent Impairments in Trace Conditioning

Recent studies have revealed that the adolescent brain may be especially vulnerable to ethanol-induced toxicity. Corticolimbic regions are more severely damaged following ethanol exposure during adolescence than during adulthood. The consequences of adolescent ethanol exposure on cognition however, have only recently begun to be explored. Male and female rats were administered 0, 1.5, 2.5 or 4.5 g/kg ethanol (20% v/v) by acute intragastric gavage during adolescence (postnatal days [PD] 28, 30, 32 and 34). On PD 40, half of the subjects in each dose group were given 5 pairings of a 10-sec flashing light (CS; conditioned stimulus) immediately followed by mild footshock (US; unconditioned stimulus), a procedure known as delay conditioning. The other half were also given 5 CS-US pairings, but the US was presented 10 sec after CS offset, a procedure known as trace conditioning. All subjects were tested for CS-elicited freezing 24 h later. There was no effect of adolescent ethanol exposure on delay conditioned responding, with all subjects demonstrating comparable levels of CS-elicited freezing. In contrast, the amount of freezing in the trace conditioned subjects was negatively correlated with prior ethanol dose. Specifically, exposure to 2.5 or 4.5 g/kg during adolescence resulted in a deficit in trace conditioned responding. These data indicate that intermittent exposure to ethanol during adolescence results in impairment in hippocampal-dependent trace conditioning that persists beyond the period of ethanol exposure. Delay conditioning was unaffected by prior ethanol treatment, indicating that there was no difficulty in detecting the CS or US, or in the ability to engage in freezing behavior. These results suggest that the adolescent brain may be particularly vulnerable to the effects of repeated exposure to ethanol that can have consequences for nonspatial, hippocampal-dependent cognitive abilities.

Effects of adolescent ethanol exposure on ethanol consumption in adult rats

Ethanol exposure during early development could predispose an individual to increased ethanol consumption. Given the high prevalence of adolescent ethanol abuse, it is important to assess the potential impact of adolescent ethanol exposure on the development of alcohol drinking. The following study was designed to assess the initiation of ethanol consumption in adult rats after exposure to ethanol vapors during adolescence. Male Sprague–Dawley rats ( n = 23) were exposed to ethanol vapor for 12 h per day for 10 consecutive days between postnatal days 30 and 40. Ethanol vapor exposure maintained blood ethanol levels averaging 250 mg/dl. All rats were subsequently trained to self-administer ethanol after a 52-day withdrawal period. When ethanol consumption was assessed in the adult rats (>3 months old) there were no significant differences in initiation or maintenance of ethanol self-administration between ethanol-exposed and control rats. In addition, there were no group differences in the ability of a noise stressor presented before the drinking session to transiently decrease ethanol intake. Overall, these findings indicate that forced exposure to ethanol vapor during adolescence does not seem to be sufficient to alter initiation or maintenance of limited-access ethanol self-administration.