Effects of Saline Substitution on Responding and Plasma Corticosterone in Rats Trained to Self-Administer Different Doses of Cocaine

Research from our laboratory has explored the role of the hypothalamo-pituitary-adrenal (HPA) axis in cocaine reinforce-ment. These experiments were designed to determine the in-volvement of the HPA axis in extinction. Male Wistar rats were trained to self-administer cocaine [0.125, 0.25, or 0.5 mg/kg/ infusion (inf)] and food pellets (45 mg) under a multiple, alter-nating schedule of reinforcement. When self-administration was stable, saline was substituted for cocaine. Blood samples were taken at the end of the sessions following cocaine self-administration, the first exposure to saline substitution (first); and once the criteria for extinction were met (final). Plasma corticosterone was measured using radioimmunoassays. Al-though there was a significant increase in the number of infu-sions obtained during the first saline substitution test by rats trained with 0.5 mg/kg/inf of cocaine, there was a decrease in infusions received when 0.125 mg/kg/inf of cocaine was tested. Following repeated exposure to the extinction conditions, re-sponding by rats trained to self-administer all three doses of cocaine was decreased to similar levels. In addition, there were significant differences in plasma corticosterone in rats trained with different doses of cocaine. Lever-pressing behavior and plasma corticosterone varied during extinction in relation to the training dose of cocaine and according to whether the rats had been exposed to single or repeated extinction testing. These data are discussed in terms of the potential difficulties involved in interpreting the effects of compounds intended to reduce drug reinforcement. There has been a substantial amount of published litera-ture devoted to the drug self-administration methodology in animals as an experimental model of human drug abus