Ethanol-paired cues elicit classical conditioning of the corticosterone response in male and female adolescent rats

TERRENCE DEAK; PAUTASSI R.M.; BARNEY, R.M.; VORE, A.S.; ANNY GANO

San Diego

Congreso; 2018 Meeting of the Research Society on Alcoholism (RSA); 2018

Research Society on Alcoholism (RSA)

cute ethanol exposure activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in a robustcorticosterone response, yet no studies have examined whether cues (context, taste, odor) associatedwith ethanol exposure might elicit a conditioned corticosterone response. Given the emergingrole of corticosterone in Alcohol Use Disorders (AUDs), we used a single-trial learning paradigm toexamine the role of ethanol-paired cues in the development of corticosterone conditioning in maleand female adolescent rats (P33?40). In the first experiment, female rats (N = 48; 6?9 per group)were exposed to a conditioned taste aversion (CTA) paradigm that paired olfactory and gustatorycues with a range of ethanol doses (1, 2, or 4 g/kg intraperitoneal [i.p.]) in a prolonged (3.5 h) contextexposure. 72 h later, subjects were injected with vehicle (0.5 g/kg) and re-exposed to the context for3.5 h. Compared to controls (4 g/kg explicitly unpaired and 0 g/kg paired groups), CTA manifestedin a dose-dependentmanner, with aversion shown in the 2 g/kg and 4 g/kg groups. Interestingly, the2 g/kg group also displayed a conditioned corticosterone response to the CTA context. To furtherexplore this effect, the second experiment utilized bothmale and female rats (N = 48; 8 per group).Rats were given ethanol (2 g/kg i.p.) paired or explicitly unpaired with a 3 h exposure to a scentedcontext, while a home cage control remained unmanipulated. On the test day, baseline tail bloodsamples were collected. Paired and unpaired groups were then given a vehicle injection and placedin the context for 3 h, and blood samples were collected 22, 45, 90, and 180 min into context exposure.Both context-exposed groups showed elevated corticosterone levels as compared to controls.In males, a significant conditioned elevation of corticosterone was observed at 22 min in the pairedgroup, indicating that ethanol-associated cues potentiated the corticosterone response to the context.Although a similar trend was observed in females, the effect approached but did not achieve significance,indicating that the vulnerability to drug-associated HPA learning may be sex-specific.These findings may provide important insight into how ethanol-paired cues might potentiate stresshormones such as corticosterone and ultimately contribute to the development of AUDs.