Operant self-administration of sweetened ethanol and time course of blood ethanol levels in adolescent and adult male Long-Evans rats.

Abstract

Little is known regarding mechanisms regulating ethanol (EtOH) self-administration during adolescence or if the mechanisms differ from adults. One of the best models of abuse liability is operant self-administration. Therefore, we characterized operant sweetened EtOH self-administration behavior in adolescent and adult rats. Adolescent (36 days old at first EtOH exposure) and adult male Long-Evans rats were first trained to self-administer 10% sucrose (10S) in an appetitive/consummatory operant model for 1 week, and then the drinking solution was switched to 10% sucrose plus 10% EtOH (10S10E) for 2 weeks. Next, rats were switched to a fixed ratio 2 schedule, and this was followed by 1 session using a progressive ratio schedule of reinforcement. Last, rats were tested for cue-induced reinstatement of lever-pressing behavior under extinction conditions after 13 days of abstinence. Blood EtOH concentration (BEC) of sweetened EtOH (self-administered or intragastric [IG] administration of 1 g/kg) was determined via gas chromatography. Control rats drank only 10S. Consumption of sweetened EtOH was not different between adolescents and adults under any schedule tested, reaching 1 g/kg in 20 minutes in the appetitive/consummatory model. Appetitive behavior directed at sweetened EtOH was less focused in adolescents versus adults. No age differences were found in motivation for sweetened EtOH. Cue-induced reinstatement of EtOH-seeking behavior after abstinence also did not differ by age. In control groups, no age difference was found in appetitive behavior or the amount of sucrose consumed, although adults exhibited greater cue-induced reinstatement. BEC after self-administration or IG administration of sweetened EtOH was higher in adults than adolescents. Consumption and motivation for sweetened EtOH are similar in adolescents and adults, although adolescents are more vulnerable to the effects of EtOH consumption on appetitive behavior. The IG results suggest larger volume of distribution and higher first-pass metabolism of sweetened EtOH in adolescents versus adults, which may limit the reinforcing effects of EtOH in some adolescents. Overall, we have begun to establish an operant sweetened EtOH self-administration model in adolescent rats.