Alcohol gains access to appetitive learning through adolescent heavy drinking.

Abstract

Adolescent heavy alcohol drinking increases the risk for alcohol use disorders in adulthood, yet mechanisms conferring increased risk are not well understood. We propose that adolescent alcohol drinking shapes alcohol’s aversive or appetitive properties in adulthood. Alcohol normally drives aversive learning and alcohol-predictive cues are avoided. We hypothesize that through adolescent heavy drinking alcohol gains access to appetitive learning. A primary consequence is that alcohol-predictive cues become valued and sought out. To test this hypothesis, we gave genetically heterogeneous, male Long Evans rats voluntary, chronic intermittent access to water or alcohol throughout adolescence and then identified moderate and heavy alcohol drinkers. After a short abstinence period, we assessed the aversive or appetitive properties of alcohol using flavor learning procedures. We compared alcohol to the known appetitive properties of sugar. Flavor learning in adult rats who were alcohol-naïve or adolescent moderate alcohol drinkers revealed alcohol to be aversive and sugar to be appetitive. The same flavor learning procedures revealed both alcohol and sugar to be appetitive in adult rats who were adolescent heavy drinkers. The results demonstrate that alcohol gains access to neurobehavioral circuits for appetitive learning through adolescent heavy alcohol drinking.

Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders

“…Consistent with previous findings from our lab [ 5 , 7 ], alcohol drinking by bodyweight was highest during initial access, declined and then stabilized over the 16 sessions of voluntary access ( Figure 2 A, sessions 1–16). In support, the ANOVA for alcohol drinking (g/kg/24 h) with lesion (control vs. BLAx) and session (1–16) as factors, found a significant main effect of session ( F 15,330 = 6.43, p < 0.01).…”

“…Adolescent alcohol drinking, particularly heavy drinking, is associated with increased risk for the development of alcohol use disorder in adulthood [ 2 , 3 ]. Consistent with observations in people, recent studies in rodents have shown that voluntary alcohol drinking in adolescence can increase alcohol drinking [ 4 ] or permit alcohol access to appetitive learning [ 5 ] in adulthood. While adolescents appear to be potentially more vulnerable to the effects of alcohol [ 6 ], the precise neural mechanisms that mediate this vulnerability have yet to be determined.…”

“…Starting on postnatal day 23 ± 3, half of the rats (24/48) were given voluntary intermittent access to alcohol (20% ethanol, v/v ). Voluntary intermittent access was based off a procedure developed by Simms and colleagues [ 15 ] and was identical to access previously used by our laboratory [ 5 , 7 ]. Experimental bottles were filled with ~40 mL of 20% ethanol, and placed on the cage at 10:30 a.m. on Sunday, Tuesday, and Thursday.…”

Lateral orbitofrontal cortex partitions mechanisms for fear regulation and alcohol consumption

“…However, differences in observed drinking patterns are not uncommon and can be due to a variety of methodological differences such as age, bottle type, housing conditions, and the nature of previous alcohol experience [ 25 , 44 ]. The pattern we observed is highly consistent with previous reports from our laboratory irrespective of [ 27 , 45 , 46 ] and following fear discrimination [ 47 ]. OF course, we cannot rule out that prior fear conditioning influenced alcohol consumption.…”

Subsecond fear discrimination in rats: adult impairment in adolescent heavy alcohol drinkers

“…Heavy drinkers (n ¼ 8, Fig. 1B) were identified as rats whose mean alcohol drinking over the final four sessions was at least 10 g/kg per 24 h. This alcoholdrinking amount is comparable with the amount of drinking demonstrated by alcohol-preferring rat strains (Marchant et al 2013), is double terminal alcohol-drinking amounts observed in adult long evans rats (Simms et al 2008), and is similar to alcoholdrinking amounts necessary to observe positive alcohol reinforcement (DiLeo et al 2015). To control for access to alcohol, the eight rats showing the lowest alcohol drinking were identified as mod-erate drinkers (Fig.…”