Sexual experience alters D1 receptor-mediated cyclic AMP production in the nucleus accumbens of female Syrian hamsters

Drugs of abuse produce long-term changes in dopamine neurotransmission and receptor-effected intracellular signaling. Similar changes in neuronal activity are mediated by motivated behaviors. To explore cellular mechanisms underlying these neuroadaptations following sexual experience, cyclic AMP accumulation following stimulation of D1 dopamine receptors, G-proteins, and adenylate cyclase was compared in the nucleus accumbens and caudate nucleus of sexually naive and experienced female hamsters following sexual behavior. Direct stimulation of adenylate cyclase with forskolin or indirectly by activation of G-proteins with Gpp(NH)p produced dose-dependent increases in the formation of cyclic AMP in the nucleus accumbens and caudate nucleus, with no effects of sexual experience on these measures. Specific D1 receptor stimulation increased Gpp(NH)p-induced adenylate cyclase activity in the nucleus accumbens and caudate nucleus of all animals. Interestingly, this stimulation was further enhanced only in membranes from the nucleus accumbens, but not from the caudate nucleus, of sexually experienced hamsters compared to the response of naive females. These results demonstrate that sexual behavior experience can sensitize mesolimbic dopamine pathways and that this sensitization occurs through an increase in D1 receptor-mediated signaling.