INTERACTION BETWEEN EXCITATORY AND INHIBITORY AMINO-ACIDS IN THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS IN INDUCING HYPERRUNNING

We have previously shown that blockade of neurotransmission mediated by gamma-aminobutyric acid (GABA) in the ventromedial nucleus of the hypothalamus (VMH) by the microinjection of a GABA(A) receptor antagonist, bicuculline methiodide (BM), exclusively induced running activity in the rat. The purpose of the present study was to examine the role of receptors for excitatory amino acids (EAAs) in the VMH in inducing hyper-running and to clarify the interaction between GABA and EAAs in the VMH in controlling running activity. Although the injection of neither N-methyl-D-aspartate (NMDA) nor quisqualate into the VMH induced hyper-running, kainate (KA) produced running activity in a dose-dependent manner with similar features to that induced by BM. This effect of KA was blocked by a non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX). GABA injected simultaneously with KA into the VMH failed to affect hyper-running induced by KA. On the other hand, DNQX significantly suppressed the BM-induced running activity. These results suggest that endogenous EAAs acting on the KA-type receptor in the VMH facilitates running activity and that the release of such EAAs from the nerve terminal is presynaptically inhibited by GABA.