MECHANISMS SUBSERVING THE STIMULATORY AND INHIBITORY COMPONENTS OF GAMMA-AMINOBUTYRIC ACID-ERGIC CONTROL OF PROLACTIN SECRETION IN THE RAT

Recently, the existence of a dual γ-aminobutyric acid (GABA)-ergic control of PRL secretion, one stimulatory exerted via the central nervous system, the other inhibitory, occurring at the level of the anterior pituitary (AP), has been envisioned. In the present study, new data are provided on the mechanisms subserving the peripheral inhibitory and central stimulatory components of GABA action on PRL release. In ovariectomized, estrogen-primed rats, iv injection of the specific peripheral GABA antagonist, bicuculline methiodide, completely blocked the inhibitory effect of muscimol (M), a specific GABA agonist, on the estrogen-induced plasma PRL rise. Direct instillation of ethanolamine-O-sulfate (EOS), a specific inhibitor of GABA transaminase (GABA-T), into the medial basal hypothalamus of freely moving male rats induced a clear-cut rise in hypothalamic and AP GABA concentrations and a striking lowering of baseline PRL levels. Intraventricular (IVT) administration of EOS (400 μg/rat) did not decrease GABA-T in the AP but only in the hypothalamus and the posterior lobe. M injected by the IVT route stimulated PRL release in unanesthetized male rats. Pretreatment with naloxone, a specific opiate receptor antagonist, or pilocarpine, a muscarinic receptor agonist, failed to impair the PRL-releasing effect of M, while blockade of cathecholamine synthesis by α-methylparatyrosine or their depletion by reserpine significantly inhibited it. In addition, IVT administration of M significantly reduced dopamine concentrations in the AP, a reliable indicator of tuberoinfundibular dopamine function. Pretreatment with 5,6-dihydroxytryptamine, a drug toxic to the serotoninergic (5-HT) system, failed to alter the PRL-releasing effect of M, while quipazine, a 5-HT receptor agonist, partially reduced the effect of M on PRL release. These data provide new information on the existence and mechanisms of action of two distinct components of GABA action on PRL secretion. It appears that 1) pituitary GABA receptors play a major role in the inhibition of PRL release induced by the peripheral administration of M; 2) the inhibitory effect of EOS injected into the mediobasal hypothalamus on PRL release results from an inhibition of GABA catabolism in a pathway which projects from the mediobasal hypothalamus to the median eminence and not from blockade of GABA-T in the AP gland; and 3) the central stimulatory component of GABA action acts via inhibition of the tuberoinfundibular dopamine system, without excluding the possibility of a participation of the 5-HT system.