RESUMO
Adolescent binge-like alcohol exposure impairs cognitive function and decision making in adulthood and may be associated with dysfunction of threat avoidance, a critical mechanism of survival which relies upon executive function. The present study investigated the impact of binge-like alcohol exposure during adolescence on active avoidance in adulthood. Male and female rats were subjected to adolescent intermittent ethanol (AIE) exposure by vapor inhalation and then tested in adulthood using a platform-mediated avoidance task. After training to press a lever to receive a sucrose reward, the rats were conditioned to a tone that co-terminated with a foot-shock. A motivational conflict was introduced by the presence of an escape platform that isolated the rat from the shock, but also prevented access to the sucrose reward while the rat was on the platform. During the task training phase, both male and female rats exhibited progressive increases in active avoidance (platform escape) in response to the conditioned tone, whereas innate fear behavior (freezing) remained relatively constant over training days. A history of AIE exposure did not impact either active avoidance or freezing behavior during task acquisition. On the test day following platform acquisition training, female rats exhibited higher levels of both active avoidance and freezing compared to male rats, while AIE-exposed male but not female rats exhibited significantly greater levels of active avoidance compared to controls. In contrast, neither male nor female AIE-exposed rats exhibited alterations in freezing compared to controls. Following 5 days of extinction training, female rats continued to display higher levels of active avoidance and freezing during tone presentation compared to males. Male AIE-exposed rats also had higher levels of both active avoidance and freezing compared to the male control rats. Together, the results demonstrate that female rats exhibit elevated levels of active avoidance and freezing compared to males and further reveal a sex-specific impact of AIE on threat responding in adulthood.
RESUMO
BACKGROUND: People with alcohol use disorders exhibit an overreliance on habitual response strategies which may result from a history of chronic alcohol exposure. Although habits are defined by behavior that persists despite changes in outcome value and in action-outcome relationships, most research investigating the effects of ethanol exposure on habits has focused only on outcome devaluation. A clear understanding of the effects of chronic alcohol exposure on the ability to flexibly update behavior may provide insight into the behavioral deficits that characterize alcohol use disorders. METHODS: To dissociate the effects of chronic intermittent ethanol (CIE) exposure on contingency-mediated sucrose versus ethanol seeking, adult male C57Bl/6J mice were assigned to 2 separate experiments. In the first experiment, mice were trained to self-administer ethanol prior to 2 cycles of interleaved CIE exposure by vapor inhalation. In a second experiment, mice were trained to self-administer sucrose and ethanol in separate training sessions prior to 4 cycles of interleaved CIE. The use of contingencies to mediate reward seeking was assessed using a contingency degradation paradigm. RESULTS: In mice trained to self-administer only ethanol, 2 weeks of CIE resulted in escalated self-administration. At this time point, CIE-exposed mice, but not air-exposed controls, exhibited ethanol seeking that was insensitive to changes in action-outcome contingency, consistent with habitual ethanol seeking. In mice trained to self-administer ethanol and sucrose rewards in sequential sessions, no escalation in self-administration across 4 weeks of CIE was observed. Under these conditions, neither Air- nor CIE-exposed mice reduced ethanol seeking in response to contingency degradation. In contrast, sucrose seeking remained goal-directed. CONCLUSIONS: Our results suggest that chronic ethanol exposure impairs contingency-driven ethanol seeking more readily than sucrose-seeking behavior. Further, these findings indicate that the transition from contingency-mediated ethanol seeking occurs more rapidly than for sucrose seeking under similar ethanol exposure conditions.
