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

Abstract

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 involved have not been ascertained. Both GABA A and GABA B receptor agonists and/or antagonists were administered centrally in this study and their effects on both basal and diurnal changes of tuberoinfundibular dopaminergic (TIDA) 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. Muscimol (1 ng/3 μl/rat, icv), a GABA A receptor agonist, but not baclofen (1–100 ng/3 μl/rat, icv), a GABA B receptor agonist, injected in the morning significantly lowered and elevated ME DOPAC and serum PRL levels, respectively at 15 and 30 min. Lower and higher doses of muscimol were not effective. The effects of muscimol could also be prevented by co-administration of bicuculline (0.1–10 ng/3 μl, icv), a GABA A receptor antagonist. When bicuculline (10–500 ng/3 μl, 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 basal and diurnal changes of TIDA neuronal activity, and in turn, PRL secretion.