Chronic sulpiride treatment produces supersensitivity of striatal adenylate cyclase to dopamine in sexually immature or adult castrated rats

Sulpiride, a substituted benzamide antipsychotic drug, is considered to be a selective antagonist at dopamine D-2 receptors, largely because it does not inhibit dopamine-stimulated adenylate cyclase activity. It was found that sulpiride in vitro can block dopamine-stimulated adenylate cyclase activity in rat striatum from sexually immature or adult castrated male rats. Chronic treatment with sulpiride (20 mg/kg i.p. twice daily for 15 days) resulted in supersensitivity of dopamine-stimulated adenylate cyclase activity in striatum from sexually immature (3-4 weeks old) as well as adult castrated rats. The apparent K[a] was decreased 4-fold in the sulpiride-treated animals, whereas the apparent V[max] remained unchanged. This treatment did not alter dopamine-stimulated adenylate cyclase activity in the striatum from adult male rats. Acute treatment with sulpiride was slightly inhibitory to dopamine-stimulated adenylate cyclase in striatum from the immature rat, suggesting that the supersensitivity after repeated injections could be a compensatory increase. In in vitro studies it was found that sulpiride at nanomolar levels could inhibit the ability of low concentrations of dopamine to stimulate adenylate cyclase activity in striatal particulate fractions from sexually immature or adult castrated rats. Sulpiride did not affect dopamine-stimulated adenylate cyclase in the adult rat striatum. Our results indicate that sulpiride can affect dopamine-stimulated adenylate cyclase activity in animals that are lacking testosterone, or perhaps estrogen. This suggests that sex hormones could regulate the sensitivity and pharmacological profile of dopamine receptors for their ligands.