The effect of adolescent ethanol exposure on cocaine reward, aversion and self-administration in adult rats.

Rationale. Ethanol is the most commonly used drug in adolescence, and ethanol use generally precedes the use of other drugs later in life. The present study explored how adolescent ethanol exposure may alter cocaine reward, aversion and self-administration later in adulthood.Methods. Male rats were exposed to ethanol (2 g/kg) or vehicle on postnatal days (PND) 30-39. On PND 65, animals began place preference conditioning (Experiment 1), taste aversion conditioning (Experiment 2) or self-administration training for food and cocaine (Experiment 3). In Experiment 1, baseline preferences were determined and then subjects underwent conditioning with 5, 10 or 20 mg/kg cocaine followed by a final preference test. In Experiment 2, subjects were given saccharin followed by injections of cocaine (32 mg/kg) or saline 15, 180 or 300 min later. In Experiment 3, subjects were given operant training sessions for food as well as two sessions on a progressive ratio (PR) schedule. After catheter surgery, subjects were given 10 self-administration training sessions (0.25 or 0.75 mg/kg/infusion) and two PR sessions for cocaine.Results. In Experiment 1, vehicle-preexposed subjects conditioned with 20 mg/kg cocaine increased time spent on the drug-paired side. Place preferences were evident at 10 mg/kg cocaine in ethanol-preexposed animals. For Experiment 2, animals exposed to vehicle during adolescence displayed a reduction in saccharin consumption at all delays. Animals exposed to ethanol displayed aversions only at the shorter delays (15 or 180 min). In Experiment 3, during the food PR sessions, vehicle-preexposed animals had more responses than animals preexposed to ethanol. Across the cocaine acquisition trials, subjects preexposed to ethanol and given 0.25 mg/kg/infusion had fewer responses and took significantly less drug during the sessions. There were no differences among groups during the cocaine PR sessions.Conclusions. Adolescent ethanol exposure sensitized the rewarding effects (Experiment 1) and attenuated the aversive effects (Experiment 2) of cocaine. Further, ethanol decreased PR responding for food as well as decreased responding for cocaine (Experiment 3) indicating changes in the sensitivity to food and cocaine. These results suggest that adolescent ethanol preexposure impacts the affective properties of cocaine that may affect later vulnerability to cocaine use.