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 nucleus of hypothalamus (VMH), has been proposed to help mediate estrogenic action on lordosis behavior by acting on midbrain periaqueductal gray (PAG) neurons. Also, in the PAG, GABA may locally regulate the levels of lordosis behavior through GABAA receptors. Therefore, we examined the effects of both Met-enkephalin and GABA-related agents on neuronal activity of PAG neurons in slices. Overall, 72.6% of the PAG neurons were inhibited by GABA and 60.9% of GABA-responsive neurons were also excited by the GABAA receptor antagonist, bicuculline methiodide (BMI), suggesting that many of GABA-responsive PAG neurons are tonically inhibited by GABAergic neurons through GABAA receptors. Dorsal PAG neurons were more responsive to BMI than ventral PAG neurons. Moreover, in the middle part of the dorsal PAG, where prominent inhibitory behavioral effects of BMI have been reported, BMI excited 94% of GABA-responsive PAG neurons from estrogen-treated animals, significantly more than observed in ovariectomized control (50%). The most frequent action of Met-enkephalin on PAG neurons was inhibitory (38 out of 149 recorded neurons) although it excited 12 neurons. A dose-dependent increase of inhibitory action of enkephalin was found in the estrogen-primed group but not in the ovariectomized control group while higher doses of enkephalin failed to excite any more neurons in both groups. Most frequently (90%), enkephalin inhibited the same neurons as those on which GABA had the inhibitory effects. Conversely, these neurons composed about 50% of the entire GABA-responsive PAG neurons. Moreover, 76% of neurons inhibited by enkephalin were found to be tonically inhibited by endogenous GABA through GABAA receptors. It is argued, therefore, that increased enkephalinergic influences from the VMH to the PAG in estrogen-treated females could participate in the PAG neuronal control of lordosis by acting on the same neurons as are innervated by intrinsic GABAergic neurons. Since GABAA agonists actually facilitate lordosis in the PAG, these PAG neurons inhibited by both GABA and enkephalin may themselves facilitate behaviors which are antagonistic to lordosis, such as defensive behaviors.