The role of D₁ and D₂ receptors in the cocaine conditioned place preference of male and female rats

The rewarding effects of cocaine have been shown to be sexually dimorphic; female rats develop cocaine conditioned place preference at lower doses and with fewer cocaine pairings than male rats. The present study was conducted to determine whether D₁ and D₂ receptors contribute to sex differences in cocaine conditioned place preference using a 4-day paradigm. Fifteen minutes prior to receiving saline or cocaine (5 mg/kg for females and 20 mg/kg for males), rats were pretreated with either SCH 23390, a D₁ receptor antagonist, (0.10, 0.25, or 0.50 mg/kg), eticlopride, a D₂ receptor antagonist, (0.05, 0.10, or 0.25 mg/kg), or vehicle (saline). Antagonism of D₁ receptors by SCH 23390 fully blocked cocaine conditioned place preference in male rats, while only the two lower doses of SCH 23390 blocked cocaine conditioned place preference in female rats. Conversely, antagonism of D₂ receptors using eticlopride had no effect on cocaine conditioned place preference in male or female rats. Due to the known role of D₁ receptors in cocaine conditioned place preference, sex differences in D₁ receptor sensitivity may explain the differences observed in cocaine reward between male and female rats.