Sexual differences in kappa opioid receptor-mediated regulation of tuberoinfundibular dopaminergic neurons

The purpose of the present study was to examine the acute effects of kappa opioid receptor blockade or activation on the activity of tuberoinfundibular dopaminergic (TIDA) neurons in gonadally-intact or castrated male and female rats. In the absence of drug treatment, the basal activity of TIDA neurons (accumulation of 3,4-dihydroxyphenylalanine, DOPA, in the median eminence after administration of a decarboxylase inhibitor) in male rats was approximately one third of that in diestrous females. In male rats, blockade of kappa opioid receptors following administration of the kappa antagonist norbinaltorphimine (NOR-BNI) increased the activity of TIDA neurons suggesting that these neurons are tonically inhibited by endogenous kappa opioids. By contrast, NOR-BNI had no effect on TIDA neuronal activity in gonadally-intact diestrous female rats, but increased the activity of these neurons in ovariectomized female rats. These results suggest that ovarian hormones block the inhibitory effects of endogenous kappa opioids on the activity of TIDA neurons. Activation of kappa opioid receptors following administration of the kappa agonist U-50,488 caused a dose-related decrease in TIDA neuronal activity in diestrous female rats. U-50,488 had no effect on TIDA neuronal activity in gonadally-intact male rats, but decreased the activity of these neurons in orchidectomized male rats. Taken together, these results reveal a sexual difference in the responsiveness of TIDA neurons to kappa opioid receptor agonists and antagonists, and suggest that gonadal steroid-induced gender differences in the basal activity of TIDA neurons may be due, in part, to differences in tonic inhibitory regulation of these neurons by endogenous kappa opioids.