Involvement of central GABAergic neurons in basal and diurnal changes of tuberoinfundibular dopaminergic neuronal activity and prolactin secretion

Central administration of gamma-aminobutyric acid (GABA) has been shown to stimulate the secretion of prolactin (PRL), Whether GABA acts via dopamine, the major PRL-inhibiting hormone, and which GABA receptor type(s) is invol ved have not been ascertained. Both GABA(A) and GABA(B) receptor agonists a nd/or antagonists were administered centrally in this study and their effec ts on both basal and diurnal changes of tuberoinfundibular dopaminergic (TI DA) neuronal activity were determined by measuring the concentration of 3,4 -dihydroxyphenylacetic acid (DOPAC) in the median eminence (ME). Serum PRL level was determined by RIA. Ovariectomized, estrogen-primed Sprague-Dawley rats implanted with intracerebroventricular (icv) cannulae were used. Musc imol (1 ng/3 mul/rat, icv), a GABA(A) receptor agonist, but not baclofen (1 -100 ng/3 mul/rat, icv), a GABA(A) receptor agonist, injected in the mornin gs significantly lowered and elevated ME DOPAC and serum PRL levels, respec tively at 15 and 30 min. Lower and higher doses of muscimol were not effect ive. The effects of muscimol could also be prevented by co-administration o f bicuculline (0.1-10 ng/3 mul/3, icv), a GABA(A) receptor antagonist. When bicuculline (10-500 ng/3 mul, icv) was given in the afternoon (at 1500 h), it significantly reversed the lowered ME DOPAC level in the afternoon and prevented the concurrent PRL surge. We conclude that endogenous GABA acting through GABA(A) receptors may play a significant role in the control of ba sal and diurnal changes of TIDA neuronal activity, and in turn, PRL secreti on. (C) 2001 Elsevier Science Inc. All rights reserved.