Sex differences in dopamine D2-like receptor-mediated G-protein activation in the medial prefrontal cortex after cocaine.

Introduction: Sexually dimorphic behavioral responses to cocaine have been linked to a difference in activation of dopamine receptors. Our study was conducted to determine whether dopamine D2-like receptor-activated G-protein contributes to sex differences in response to cocaine in the medial prefrontal cortex (mPFC).

Method: In vitro functional autoradiography was performed using dopamine receptor D2 agonist (quinpirole, 100 microM) to stimulate [35S]GTPgammaS binding in brain tissue sections from male and female Fischer rats treated with saline (1 mL/kg) or cocaine (20 mg/kg; i.p.).

Results: Overall, quinpirole increased G-protein activation in the caudate-putamen, nucleus accumbens, and frontal cortex in both sexes. Although saline-treated male rats had higher [35S]GTPyS binding in the mPFC than their female counterparts, cocaine-treated females had higher [35S]GTPgammaS binding in the mPFC than cocaine-treated males.

Conclusions: These data suggest that both intrinsic and activational effects of dopamine D2-like receptor-mediated G-protein activation in the mPFC may contribute to the differences between males and females in their response to acute cocaine administration.