Age-Related Differences in Alcohol Intake and Control Over Alcohol Seeking in Rats

Abstract

Alcohol use disorder (AUD) is characterized by excessive and persistent alcohol use, despite adverse consequences. AUD often originates during adolescence, as do other substance use disorders. However, despite periods of excessive alcohol intake, many adolescents reduce their alcohol use by early adulthood. Brain development, social context, personality traits, and genetic makeup are thought to play an important role in these age-dependent fluctuations in alcohol use. However, studies that directly investigate age-related differences in the effects of alcohol exposure on brain and behavior are sparse. Therefore, to better understand the relationship between adolescent alcohol consumption and AUD-like behavior, this study compared the degree of control over alcohol seeking in rats that differed in terms of age of onset of alcohol drinking and in their level of alcohol consumption. We hypothesized that control over alcohol seeking is more prominent in adolescent-onset rats than in adult-onset rats, and that control over alcohol seeking is related to the consumed amount of alcohol. To test this hypothesis, alcohol seeking in the presence of a conditioned aversive stimulus was assessed after 2 months of intermittent alcohol access (IAA) in rats that consumed alcohol from postnatal day 42 (adolescence) or day 77 (adulthood). The rats were subdivided into low (LD), medium (MD), or high (HD) alcohol drinking rats, in order to assess the impact of the extent of alcohol intake on control over alcohol seeking. The adolescent-onset animals consumed slightly, but significantly less alcohol compared to the adult-onset rats. In adult-onset rats, we found that conditioned suppression of alcohol seeking, i.e., reduction of alcohol seeking by presentation of a conditioned aversive stimulus, was most pronounced in LD. By contrast, in the adolescent-onset rats, MD and HD showed increased alcohol seeking compared to LD, which was suppressed by conditioned aversive stimuli. Taken together, these findings reveal a complex relationship between the age of onset and level of alcohol intake with control over alcohol seeking, whereby adolescent rats consume less alcohol than adults. In adult rats, control over alcohol seeking is negatively related to preceding levels of alcohol intake. By contrast, adolescent rats appear to retain control over alcohol seeking, even after a history of high levels of alcohol intake.

Keywords: addiction-like behavior; adolescence; alcohol; conditioned suppression; individual differences; loss of control; rats.

Figure 1

Alcohol intake in adolescent onset and adulthood onset rats. Depicted are alcohol intake (A), alcohol preference (B), and total volume (V) of fluid consumed (C) for selected low drinkers (LD), medium drinkers (MD), and high drinkers (HD) from both age groups. The data are shown as mean + SEM. ***Significant overall difference between adolescent-onset and adult-onset rats, independent of drinking group by post-hoc pairwise comparison, (P < 0.001).

Figure 2

Responding for alcohol under FR1 (A) and RI120 (B) schedules of reinforcement. Shown are the average number of active responses during the (last) three sessions of training on the respective schedules for adolescent-onset and adult-onset low (LD), medium (MD), and high alcohol drinking (HD) rats after 8 weeks of intermittent alcohol consumption. Data are presented as mean + SEM active responses. ***MD and HD made more active responses compared to LD, independent of age group (post-hoc pairwise comparisons, P < 0.001) and ^##HD made more active responses than MD, independent of age group (post-hoc pairwise comparisons, P < 0.01).

Figure 3

Conditioned suppression of alcohol seeking in CS– and CS+ groups of adolescent-onset and adult-onset low (LD), medium (MD), and high alcohol drinking (HD) rats after 8 weeks of intermittent alcohol consumption. In (A–C), the number of active responses during consecutive CS ON and CS OFF intervals are shown for adolescent-onset LD, MD, and HD, respectively. In (D–F), the number of active responses during CS ON and CS OFF intervals are shown for adult-onset LD, MD, and HD, respectively. Data are presented as mean + SEM active responses, binned in 2 min intervals. Significant differences between CS– and CS+ groups are indicated by * and ** (post-hoc pairwise comparisons, P < 0.05 and P < 0.01, respectively).

Figure 4

Conditioned suppression of alcohol seeking in CS– and CS+ groups of adult-onset and adolescent-onset low (LD), medium (MD), and high alcohol drinking (HD) rats after 8 weeks of intermittent alcohol consumption. In (A–C), the latency to the first active response during consecutive CS ON and CS OFF intervals are shown for adolescent-onset LD, MD, and HD, respectively. In (D–F), the latencies to respond during CS ON and CS OFF intervals are shown for adult-onset LD, MD, and HD, respectively. Data are presented as mean + SEM active responses, binned in 2 min intervals. Significant differences between CS– and CS+ groups are indicated by * and** (post-hoc pairwise comparisons, P < 0.05 and P < 0.01, respectively).

Figure 5

Freezing behavior in adolescent-onset low (LD; A), medium (MD; B), and high (HD; C) alcohol drinking rats and adult-onset LD (D), MD (E), and HD (F). Shown is the duration of freezing in the conditioning chamber, expressed as a percentage of the 2 min prior to (Tone OFF) and during presentation of the footshock-associated CS+ (Tone ON) period. The conditioned rats (CS+) showed significant context- and CS-induced freezing, while the respective CS– control groups did not. This was comparable for all age and alcohol drinking groups. Data are presented as mean + SEM. ^#, ^##, ^###Significant difference between CS– and CS+ groups (post-hoc pairwise comparisons, P < 0.05, P < 0.01, and P < 0.001, respectively). ***Significant difference between tone ON and tone OFF periods (post-hoc pairwise comparisons, P < 0.001).