| Sex dependent neurochemical changes after cocaine administration could affect psychomotor activation and may be critical in the drug's rewarding/reinforcing properties. The aim of this proposal is to determine whether there are sex differences in cocaine-induced conditioned place preference (CPP), and the extent to which gonadal and adrenal hormones modulate cocaine CPP in male and female rats. To address these questions, side-by-side comparisons were conducted to determine the effects of conditioning length, cocaine dose and adrenalectomy on cocaine CPP in male and female rats. Female rats demonstrated cocaine CPP after 4 pairing sessions, while male rats required 8 pairing sessions to develop CPP for cocaine. Also, female rats developed CPP at cocaine doses of 5 and 10 mg/kg while male rats required higher cocaine doses (20 mg/kg). Overall, females had higher blood serum levels of corticosterone. Furthermore, a dose-dependent effect on serum levels of corticosterone was observed only in female rats, where rats conditioned with 20mg/kg cocaine had significantly higher serum levels of corticosterone than rats conditioned with 5mg/kg cocaine. However, adrenalectomy did not affect CPP for cocaine in either sex. These results suggest that a female's higher sensitivity to cocaine's rewarding effects is not completely mediated by the Hypothalamic-Pituitary-Adrenal (HPA) axis.; Therefore, sex differences in the acquisition and/or expression of cocaine CPP may be modulated by other mechanisms, such as the HPG axis. Although both intact and gonadectomized male and female rats showed a significant CPP for cocaine, ovariectomy attenuated the magnitude of preference. These alterations coincided with a decrease in serum levels of corticosterone. In ovariectomized rats, pretreatment with progesterone inhibited cocaine CPP while estrogen plus progesterone potentiated the magnitude of CPP. Additionally, gonadectomy and ovarian hormone replacement in female rats affected monoamine levels and turnover ratios in the ventral tegmental area and nucleus accumbens shell. While no effects of castration were observed ovariectomy decreased levels of dopamine and serotonin in the ventral tegmental area. In females, progesterone replacement increased levels of serotonin and dopamine in the ventral tegmental area while estrogen plus progesterone replacement increased dopamine levels in the nucleus accumbens. These results indicate that ovarian hormones may influence cocaine reward by altering monoaminergic systems. |
