Sexual differences in N-methyl-D-aspartate receptor-mediated regulation of tuberoinfundibular dopaminergic neurons in the rat.

The purpose of the present study was to examine the effects of N-methyl-D-aspartate (NMDA) receptor blockade on the activity of tuberoinfundibular dopaminergic (TIDA) neurons in male and female rats. TIDA neuronal activity was estimated by measuring either the accumulation of 3,4-dihydroxyphenylalanine (DOPA) 30 min after the administration of the decarboxylase inhibitor NSD-1015 or the concentration of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence. The non-competitive NMDA receptor antagonist MK-801 markedly reduced prolactin secretion in both male and female rats. MK-801 also produced a dose- and time-dependent decrease in the activity of TIDA neurons in female rats, but had no effect on the activity of TIDA neurons in either intact, orchidectomized or orchidectomized, testosterone-treated male rats. Removal of the tonic stimulatory effects of prolactin on TIDA neurons in female rats by immunoneutralization of endogenous prolactin failed to alter the responsiveness of TIDA neurons to the inhibitory effects of MK-801. On the other hand, MK-801 was unable to inhibit TIDA neurons in ovariectomized female rats, but the responsiveness of TIDA neurons to MK-801 in ovariectomized female rats was restored following estrogen replacement, even in the absence of prolactin. Like MK-801, the competitive NMDA receptor antagonist CGS-19755 produced a dose-dependent decrease in TIDA neuronal activity in female rats, which was prevented in a dose-dependent manner by the NMDA receptor agonist D,L-(tetrazol-5-yl) glycine. Taken together, these results reveal a sexual difference in the responsiveness of TIDA neurons to NMDA receptor antagonists, and suggest that estrogen positively modulates NMDA receptor-mediated, tonic stimulation of TIDA neurons in female rats by a prolactin-independent mechanism.