Effects of menstrual cycle phase on the reinforcing effects of phencyclidine (PCP) in rhesus monkeys

Substantive evidence indicates that there are sex differences in the reinforcing effects of drugs, and gonadal steroid hormones, such as estrogen and progesterone, likely contribute to these differences. Among females, subjective effects of drugs differ as a function of menstrual cycle phase. The purpose of the present study was to compare oral self-administration of phencyclidine (PCP) in female rhesus monkeys (Macaca mulatta) across different phases of the menstrual cycle. Since the 28-day menstrual cycle of non-human primates is similar to that of humans, this model could provide important evidence supporting the implication that changes in the levels of gonadal hormones across menstrual phase can alter a drug's reinforcing effects. Oral self-administration of several concentrations of PCP (0.125, 0.25, and 0.5 mg/ml) was examined in three sexually mature female monkeys during 3-h experimental sessions. Menstrual cycle phase was determined by onset of menses and verified by examining vaginal cytology. PCP self-administration was greater during the luteal phase at the 0.125 and 0.25 mg/ml concentrations, which is normally characterized by high levels of progesterone and moderate levels of estrogen, than during the follicular phase, when levels of estrogen are increasing and progesterone levels are low. When examined within each phase, numbers of PCP deliveries were highest during the mid-luteal phase, compared to the early and mid-follicular phases. No differences in self-administration were observed between early and mid-follicular phases, but a significant difference in PCP deliveries was found between mid- and late luteal phases at the lowest concentration of PCP tested. The results from this study suggest that PCP's reinforcing effects in female monkeys differ as a function of menstrual cycle phase.