IN-VITRO ELECTROPHARMACOLOGICAL AND AUTORADIOGRAPHIC ANALYSES OF MUSCARINIC RECEPTOR SUBTYPES IN RAT HYPOTHALAMIC VENTROMEDIAL NUCLEUS - IMPLICATIONS FOR CHOLINERGIC REGULATION OF LORDOSIS

Muscarinic agonists can act through the hypothalamic ventromedial nucl eus (VMN) to facilitate lordosis. To elucidate the neuronal mechanism( s) underlying this muscarinic facilitation, effects of muscarinic agen ts on the single-unit activity of VMN neurons recorded in brain tissue slices of estrogen-primed female rats were analyzed. All the agonists tested, including acetylcholine (ACh), oxotremorine-M (OM), carbachol (CCh) and McN-A-343 (McN), evoked primarily excitation (80-100%), som e inhibition (0-20%) and occasional biphasic responses (0-8%). By comp aring the response magnitude and the effectiveness in evoking a respon se, the rank order for evoking excitation, the primary response, was f ound to be: OM > CCh > ACh approximate to McN, which is consistent wit h that (OM > CCh much greater than McN) for facilitating lordosis repo rted by others. This consistency and the frequency of its occurrence s uggest that the excitatory electric action of the muscarinic agonists is related to their facilitatory behavioral effect. Experiments with a ntagonists selective for M1 (pirenzepine), M2 (AF-DX 116) and M3 (4-DA MP and p-F-HHSiD) indicate that muscarinic excitations are mediated by M1 and/or M3, but not M2. Since M1 receptors have been shown to be ne ither sufficient nor necessary to mediate the muscarinic facilitation, M3 receptor may be crucially involved in this behavioral effect. Auto radiographic assays of binding to [H-3]4-DAMP with or without pirenzep ine and AF-DX 116, also indicate the presence of M3 receptors in the V MN. Quantitative analyses show that the M3 binding was not affected by the in vivo estrogen priming required to permit muscarinic agonists t o facilitate lordosis. Thus, while the excitation mediated by M3 is li kely to be involved in muscarinic facilitation of lordosis, the regula tion of M3 receptor density does not seem to be involved in the permis sive action of estrogen.