Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress

Abstract

Background: Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed.

Methods: Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings.

Results: This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment.

Conclusions: Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption.

Figure 1

Percent Body Weight Gain Before and After 5 Days of Restraint Stress. Overall, adolescents showed greater increases in body weight across the 5 days of restraint stress than adults. Stressed animals of both ages gained significantly less weight than their non-stressed counterparts.

Figure 2

Baseline Sucrose Intake. For Experiment 1, adolescents consumed more sucrose (g/kg) than their adult counterparts. No differences in sucrose intake among stressed and non-stressed animals were observed in animals of either age. For Experiment 2, adolescents again consumed more sucrose than adults. While isolate- and pair-housed adults showed similar sucrose consumption, isolate-housed adolescents consumed significantly less sucrose than pair-housed adolescents.

Figure 3

Mean Percent Sucrose on Test Day. Adolescent subjects injected with ethanol doses of 1.5 g/kg or higher demonstrated a significant reduction compared to saline controls in percent sucrose consumed on the test day. Adult subjects injected with ethanol doses of 1.0 g/kg or higher exhibited an attenuation of percent sucrose intake on the test day.

Figure 4

Sucrose Intake Across Test Days. During the test days following the first conditioning session, adolescent animals in both housing conditions significantly reduced their sucrose intake compared to saline-injected controls following a 1.5 g/kg dose of ethanol on test days 2–4. Adult animals demonstrated a reduction in sucrose consumption on test days 1–4 following ethanol doses of 1.0 g/kg or higher.

Figure 5

Percent of Baseline Sucrose Intake Across Test Days. Across the four test days following the first conditioning session, adolescent animals in both housing conditions consumed a significantly smaller percent of their baseline sucrose intake compared to saline-injected controls on test days 3–4 following an ethanol dose of 1.5 g/kg. Adult animals, however, demonstrated a significant decrease from baseline sucrose consumption on all four test days following ethanol doses of 1.0 g/kg and higher. Adults showed a significant reduction from baseline sucrose intake compared to adolescents on test days 3–4 following conditioning with the 1.0 g/kg ethanol dose (* indicates significant difference from saline controls; + indicates significant decrease relative to adolescents).