Age- and sex-dependent amphetamine self-administration in rats

Abstract

Recreational drug use peaks in the developmental stage of adolescence, and exposure to drugs during adolescence may predict drug dependence in adulthood. Nevertheless, adolescent drug vulnerability is not widely studied in animal models of drug intake, and very few studies have investigated sex differences in drug-related behavior during adolescence. We compared patterns of intravenous (i.v.) amphetamine self-administration among adolescent vs adult, male vs female Sprague-Dawley rats on a fixed ratio (FR) followed by a progressive ratio (PR) schedule of reinforcement. After surgical implantation of i.v. catheters, adolescent [postnatal day (P) 35-52] and adult (P90-106) male and female rats were allowed to acquire lever-pressing behavior reinforced by either 0.025 or 0.05 mg/kg/0.1-ml amphetamine infusions over 14 daily 2-h sessions on an FR1 schedule (n = 9-12 per age-, sex-, and dose-group). Subsequently, responding maintained by 0.0125 or 0.05 mg/kg per infusion amphetamine in 4-h sessions on a PR schedule was tested. Adolescent rats acquired amphetamine self-administration faster than adults, reached a higher number of infusions, and took more amphetamine than their adult counterparts during the acquisition phase, although age differences varied by dose. In PR testing, young adult males earned fewer infusions than older adult males, whereas young adult females earned more infusions than their older adult counterparts, and more than age-matched males. These results suggest that i.v. amphetamine self-administration in rats is a useful model to investigate the potential neurochemical and endocrine bases for age and sex differences in vulnerability to behavioral reinforcement by amphetamine.