There is growing evidence that there are sex differences in response to drugs of abuse. However, only a limited number of studies in rodents have assessed whether there are sex differences in the reinforcing effects of opioids and the human data are sparse. Nevertheless, some of the sex differences observed can be attributed to cycling ovarian hormones in females. This proposal will parametrically evaluate the behavioral and reinforcing effects of smoked heroin across the menstrual cycle in normally-cycling adult female rhesus monkeys, Levels of estradiol (EST), progesterone (PRO) and luteinizing hormone (LH) will be routinely monitored, correlating changes in hormone levels to the behavioral effects of heroin. Exp. 1 will carefully characterize the time course of heroin blood levels across the menstrual cycle. Subsequently, heroin seeking and taking will be measured using a second-order schedule, choice and location preference procedures when the monkeys are not dependent (Exp. 2) and again (Exp. 4) when they are dependent on opioids; and the reinforcing effects of heroin will be measured using a Progressive Ratio procedure when the monkeys are not dependent (Exp. 3) and again (Exp.5) when they are dependent on opioids. These experiments will provide valuable data about changes in the behavioral and reinforcing effects of heroin across the menstrual cycle when heroin is available under non-dependent and dependent conditions. In addition, this proposal will provide important information on the effects of self-administered opioids on the regulation of the menstrual cycle. The proposed studies will be the first to systematically evaluate these effects in female non-human primates.
