Involvement of catecholamines and glutamate in GABAergic mechanism regulatory to luteinizing hormone and prolactin secretion.

There is some evidence that a population of estrogen-receptive neurons exists in the preoptic/anterior hypothalamic area which uses gamma-aminobutyric acid (GABA) as neurotransmitter and which is involved in mediating the negative feedback of estrogens on pituitary luteinizing hormone (LH) secretion. These neurons are proposed to be presynaptic inhibitors to norepinephrine (NE) release thereby inhibiting the stimulatory effect of NE on LHRH neurons. Muscimol, a potent GABA agonist, inhibits pituitary LH release in ovariectomized rats after intraventricular injection of 5 nmol. This treatment significantly increased prolactin levels. Catecholamine turnover rates in micropunches of various hypothalamic and mesolimbic structures following intraventricular treatment with muscimol were determined using the method of blocking the activity of tyrosine hydroxylase by alpha-methyl-p-tyrosine. Muscimol did not affect catecholamine, GABA and glutamate concentrations. Turnover rates of NE were significantly reduced in the medial preoptic/anterior hypothalamic area. In this structure as well as in the nucleus accumbens and in the anterior mediobasal hypothalamus turnover rates of dopamine (DA) were also reduced whereas DA turnover in mediocortical amygdalae was increased by muscimol. The selective reduction of NE turnover following muscimol may be explained by a direct or indirect action of the GABA-eric drug on NE axon terminals. The reduced NE and DA turnover in the medial preoptic area may be causally related to reduced serum LH levels whereas the reduced hypothalamic DA turnover may explain increased blood prolactin levels.