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

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).

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.).

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.

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.