The aim of this study was to elucidate the involvement of kainate (KA) type glutaminergic, GABAergic and adrenergic receptors in the ventromedial nucleus of the hypothalamus (VMH) in inducing running activity and metabolic adaptations. Injection of either KA or bicuculline methiodide (BM), a GABAA receptor antagonist, into the VMH of conscious rats resulted in an increase in plasma glucose, norepinephrine, epinephrine and corticosterone, as well as running activity. KA or BM increased plasma glucose and catecholamine even under urethane anesthesia. Co-injection of either alpha- or beta-adrenergic receptor antagonist, i.e. phentolamine or timolol, respectively, with KA into the VMH of conscious rats elicited only a slight increase in plasma glucose and catecholamines, though it successfully induced hyper-running. However, plasma corticosterone was higher in the animals injected with adrenergic blockers, suggesting that an insufficient supply of energy substrates would enhance the activity of the hypothalamo-pituitary-adrenal system. We conclude that: (1) KA type glutaminergic and GABAergic receptors in the VMH are involved in regulating running activity and the sympathetic nervous system; (2) the brain noradrenergic system may mediate the KA action on the sympathetic nervous system.