Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry

Abstract

Alcohol use increases across adolescence and is a concern in the United States. In humans, males and females consume different amounts of alcohol depending on the age of initiation, and the long-term consequences of early ethanol consumption are not readily understood. The purpose of our work was to better understand the immediate and long-term impact of ethanol exposure during adolescence and the effects it can have on behavior and dopaminergic responsivity. We have assessed sex differences in voluntary ethanol consumption during adolescence and adulthood and the influence of binge ethanol exposure during adolescence. We have observed that males are sensitive to passive social influences that mediate voluntary ethanol consumption, and early ethanol exposure induces long-term changes in responsivity to ethanol in adulthood. Exposure to moderate doses of ethanol during adolescence produced alterations in dopamine in the nucleus accumbens septi during adolescence and later in adulthood. Taken together, all of these data indicate that the adolescent brain is sensitive to the impact of early ethanol exposure during this critical developmental period.

Figure 1

The diagram is a schematic of the experimental protocol used in the social interaction experiment.

Figure 2

As depicted in the figure adolescent male alcohol naïve observer rats that socially interacted with demonstrators administered the highest dose of ethanol showed an increase in time spent in the chamber paired with social interaction with an alcohol-intoxicated demonstrator after conditioning relative to all other groups. Adolescent alcohol naïve female observers showed no change in time spent in the chamber paired with social interaction with an alcohol-intoxicated demonstrator, regardless of dose. Data presented are mean +/− SEM difference in seconds spent in the paired chamber at test minus baseline presented as the change in time spent in the chamber paired with social interaction in the adolescent alcohol naive observer’s initially least preferred chamber. * indicates significant difference from all other sex- and dose-matched groups. The bars indicate the type of demonstrator the alcohol naïve adolescent observer socially interacted with (0.0 (clear bars)- social interaction with a sober peer; 0.5 (light grey) and 1.5 (dark grey)- social interaction with an alcohol-intoxicated peer). Female 0.0 n = 13; Female 0.5 n = 14; Female 1.5 n = 13; Male 0.0 n = 8; Male 0.5 n = 11; Male 1.5 n = 10.

Figure 3

As depicted in the figure, animals that were pretreated with ethanol during adolescence and conditioned with ethanol in young adulthood spent more time in the ethanol-paired chamber relative to rats that were pretreated saline and conditioned with ethanol in young adulthood and also those that were pretreated with ethanol during adolescence and conditioned with saline in adulthood. Data presented are mean +/− SEM of the change in time spent in the paired chamber in the initially least preferred chamber (test-baseline). The bars indicate conditioning in young adulthood with saline (clear bars) or ethanol (grey bars). Saline-Saline n = 9; Saline-Ethanol n = 10; Ethanol-Saline n = 9; Ethanol-Ethanol n = 9.

Figure 4

In both panels, the x-axis denotes Age and the y-axis denotes extracellular DA levels (nM). Both approaches yielded similar age results [quantitative: F(2, 12)=14.01, P < 0.05; conventional: F(3, 279)=17.171, P < 0.05] with late adolescent animals (PND 45) having significantly higher basal DA levels than adults, but with the conventional method (Philpot and Kirstein, 2004), levels obtained in adolescents were higher than those obtained using the quantitative method (Badanich, Adler & Kirstein, 2006). Additionally, the quantitative approach revealed lower basal DA levels for early adolescent (PND 35) rats. For panel A, # = differs from PND 60; ## = differs from PND 45 and PND 60. For panel B, diamonds = differs from PND 45 and PND 60; stars = differs from all other ages. It should be noted the conventional method in panel B shows dialysate DA levels that were not corrected for probe recovery. Figures reproduced with permission from Philpot and Kirstein, 2004 and Badanich et al, 2006).

Figure 5

The amount of DA in the microdialysis perfusate (DAin) is on the x-axis while the difference between DAin and recovered DA (DAout) is on the y-axis (DAin − DAout). The broken horizontal line depicts the point of no net flux of DA between the brain and the microdialysis perfusate. The x-intercept denotes the extracellular DA concentration in the NAcc for ethanol-treated (solid line; n=4) and saline control (broken line n=4) rats. Basal DA was greater for rats pretreated with ethanol during adolescence (6.5 nM DA) than for saline controls (3.6 nM DA); [t(6)= 2.458, P < 0.05]. The slope of the regression line denotes the extraction fraction (E_d), an indirect measure of DA reuptake, for ethanol-treated (87%) and saline control (68%) rats. Each data point denotes mean and SEM. This figure has been reproduced with permission from Badanich et al., 2007.