Neuroendocrine interactions of excitatory and inhibitory amino acids

Abstract

When a non-toxic dose (25 mg/kg) of the excitatory amino acid, N-methyl aspartate (NMA), is administered SC to 25 day old male rats, serum levels of luteinizing hormone (LH) rise 8–10 fold. The LH response is rapid (within 7 1 2 min ), brief (30 min duration) and reversible. It is dependent on the integrity of arcuate hypothalamic (AH) neurons and is suprasellar, since NMA does not release LH in AH-lesioned rats nor from the pituitary in vitro. NMA, which has access to AH neurons from blood (because AH lies outside blood brain barriers), selectively destroys AH neurons when given in sufficient dose (75 mg/kg SC). We have proposed that both the toxic and LH-releasing actions are mediated by an excitatory interaction of NMA with receptors on the dendrosomal surfaces of AH neurons. Alpha-aminoadipate, an effective antagonist of NMA excitation, inhibits both the toxic and LH-releasing effects of NMA. GABA blocks NMA-induced LH release in a dose-dependent manner but does not block NMA toxicity. GABA inhibition of NMA action is antagonized by bicuculline. Our findings suggest that AH neurons are involved in gonadotrophin neuroregulation and that this system may be driven and inhibited respectively by amino acid excitatory and inhibitory transmitter inputs.