THE EFFECT OF EXCITATORY AMINO-ACIDS ON GABA RELEASE FROM MEDIOBASAL HYPOTHALAMUS OF FEMALE RATS

The purpose of the present study was to examine the in vitro effect of L-glutamate and its agonists on basal and potassium-evoked GABA relea se from incubated mediobasal hypothalamus (MBH) of intact, ovariectomi zed (OVX) and OVX-estrogenized female rats. L-glutamate (100 mu M) dec reased evoked GABA release from MBH of intact female rats in diestrus. NMDA and quisqualate (10 and 100 mu M) modified neither basal nor evo ked hypothalamic GABA release of intact rats. However, kainate (10 and 100 mu M) decreased hypothalamic basal and evoked GABA release of int act rats. Kainate induced no changes in basal or in evoked GABA releas e from hypothalami of OVX rats, but decreased GABA release in chronica lly estrogenized rats. DNQX (6,7-dinitroquinoxaline-2,3-dione), a non- NMDA receptor antagonist, failed to affect GABA release but blocked th e inhibitory effect of kainate. The kainate effect was not Mg2+-sensit ive and was not inhibited by D-AP5 (D(-)-2-amino-5-phosphonopentanoic acid), an NMDA-specific receptor antagonist. Kainate induced no change s in nitric oxide synthase activity in MBH of either intact or estroge nized rats. These data indicate that kainate decreases GABA release fr om MBH of female rats through a non-NMDA receptor subtype, and provide evidence to support the view that kainate-mediated decrease of the hy pothalamic GABAergic tone is affected by estrogens. (C) 1998 Elsevier Science Ireland Ltd.