GAMMA-AMINOBUTYRIC ACID RECEPTOR FUNCTION IN RAT ANTERIOR-PITUITARY - EVIDENCE FOR CONTROL OF PROLACTIN-RELEASE

The rise in serum PRL concentration induced by administration of haloperidol (0.05-0.5 mg/kg, iv) or morphine (2–15 mg/kg, sc) to male rats and during estrogen treatment (1 mg/day for 15 days) in ovariectomized rats was reduced by systemic injection of the γ-aminobutyric acid (GABA) receptor agonist, muscimol (1 mg/kg, iv). Intraventricular or intrahypothalamic injection of muscimol (100–500 ng) did not alter PRL release or block the PRL release induced by haloperidol or morphine; rather, a slight stimulation of PRL release was observed after intraventricular injection of a dose of 800 μl muscimol. Since the concentration of muscimol in different brain areas after central administration was similar to that after systemic injection, these observations suggested that peripheral rather than central GABA receptors were involved in blocking haloperidol- or morphine-induced PRL release. Proof that peripheral GABA receptors were involved was provided by the experiments with bicuculline methiodide. This specific GABA receptor agonist, which does not enter the brain, counteracted the action of muscimol. The high levels of muscimol in the anterior pituitary after systemic injection and its absence after central administration suggested that blockade of PRL release by muscimol might result from a stimulation of GABA receptors located in the pituitary. Indeed, [3H]muscimol and [3H]GABA receptor sites with characteristics similar to those of brain were present in rat anterior pituitary. In addition, muscimol (10-8–10-6M) reduced the spontaneous release of PRL from anterior pituitary halves in vitro. This effect was reversed by the GABA receptor antagonist, bicuculline, but not by the dopamine antagonist, sulpiride. The results provide evidence that GABA receptor stimulation in the anterior pituitary can act to regulate PRL release. © 1979 by The Endocrine Society.