Sex differences and the influence of estrogen on intravenous drug self -administration in rats.

摘要

Sex differences have been reported in animal models of drug abuse. Females are more vulnerable during transition phases of drug abuse than males. There is evidence that supports the contribution of estrogen in these sex differences. The research included in this thesis is concerned with sex differences and the influence of estrogen on the self-administration of intravenously (i.v.) delivered drugs in rats. Experiments 1a and 1b are focused on sex differences in the acquisition and maintenance of methamphetamine (METH) self-administration. The effects of sex on the acquisition of METH self-administration were examined using an autoshaping procedure, and maintenance of METH-reinforced behavior was evaluated using a progressive ratio (PR) schedule of reinforcement. In experiment 2a the influence of estrogen on the acquisition of heroin self-administration was investigated using the autoshaping procedure. Additionally, in Experiment 2b the influence of estrogen on the reinforcing strength of heroin was compared in ovariectomized (OVX) female rats with and without estrogen replacement. PR and behavioral economic measures were used to evaluate the reinforcing strength of heroin. Finally, in Experiment 3 the effects of sex on the escalation of cocaine intake were examined using a differential access paradigm. Animals were given long- (6 h) or short- (1 h) access periods of cocaine self-administration. Subsequently, access conditions were the same (3 h) for both groups and dose-response curves for cocaine were compared across groups to examine the influence of escalation of cocaine intake. Results of Experiment 1 showed that female rats were more vulnerable to the acquisition of METH self-administration compared to males. Female rats also displayed increased METH-maintained responding under the PR schedule relative to males. Results of Experiment 2 indicated that OVX female rats treated with estradiol benzoate were more vulnerable to the acquisition of heroin self-administration than untreated OVX females. Additionally, estradiol benzoate treatment enhanced the point of maximum responding (Pmax) for heroin self-administration in OVX female rats compared to untreated OVX females. Finally, in Experiment 3 female rats given long-access (6 h) to cocaine self-administration displayed a greater amount of escalation of cocaine intake than long-access (6 h) male rats.