IN-VITRO ELECTROPHYSIOLOGICAL CHARACTERIZATION OF MIDBRAIN PERIAQUEDUCTAL GRAY NEURONS IN FEMALE RATS - RESPONSES TO GABA- AND MET-ENKEPHALIN-RELATED AGENTS

Met-Enkephalin, which can be induced by estrogen in the ventromedial n ucleus of hypothalamus (VMH), has been proposed to help mediate estrog enic action on lordosis behavior by acting on midbrain periaqueductal gray (PAG) neurons. Also, in the PAG, GABA may locally regulate the le vels of lordosis behavior through GABA(A) receptors. Therefore, we exa mined the effects of both Met-enkephalin and GABA-related agents on ne uronal activity of PAG neurons in slices. Overall, 72.6% of the PAG ne urons were inhibited by GABA and 60.9% of GABA-responsive neurons were also excited by the GABA(A) receptor antagonist, bicuculline methiodi de (BMI), suggesting that many of GABA-responsive PAG neurons are toni cally inhibited by GABAergic neurons through GABA(A) receptors. Dorsal PAG neurons were more responsive to BMI than ventral PAG neurons. Mor eover, in the middle part of the dorsal PAG, where prominent inhibitor y behavioral effects of BMI have been reported, BMI excited 94% of GAB A-responsive PAG neurons from estrogen-treated animals; significantly more than observed in ovariectomized control (50%). The most frequent action of Met-enkepahlin on PAG neurons was inhibitory (38 out of 149 recorded neurons) although it excited 12 neurons. A dose-dependent inc rease of inhibitory action of enkephalin was found in the estrogen-pri med group but not in the ovariectomized control group while higher dos es of enkephalin failed to excite any more neurons in both groups. Mos t frequently (90%), enkephalin inhibited the same neurons as those on which GABA had the inhibitory effects. Conversely, these neurons compo sed about 50% of the entire GABA-responsive PAG neurons. Moreover, 76% of neurons inhibited by enkephalin were found to be tonically inhibit ed by endogenous GABA through GABA(A) receptors. It is argued, therefo re, that increased enkephalinergic influences from the VMH to the PAG in estrogen-treated females could participate in the PAG neuronal cont rol of lordosis by acting on the same neurons as are innervated by int rinsic GABAergic neurons. Since GABA(A) agonists actually facilitate l ordosis in the PAG, these PAG neurons inhibited by both GABA and enkep halin may themselves facilitate behaviors which are antagonistic to lo rdosis, such as defensive behaviors.