GABA STIMULATION OF GONADOTROPIN-II RELEASE IN GOLDFISH - INVOLVEMENT OF GABA(A) RECEPTORS, DOPAMINE, AND SEX STEROIDS

The involvement of gamma-aminobutyric acid (GABA) in regulation of pituitary gonadotropin-II (GTH-II) release was studied in the goldfish. Intraperitoneal injection of GABA (300 mug/g) stimulated an increase in serum GTH-II levels at 30 min postinjection. The GABA(A) receptor agonist muscimol (0.1-10 mug/g) stimulated GTH-II in a dose-dependent manner. Baclofen, a GABA(B) receptor agonist, had a small but significant stimulatory effect at 1 and 10 mug/g; the amount of GTH-II released in response to baclofen was significantly less (P < 0.05) than that released by muscimol. Pretreatment of goldfish with bicuculline, a GABA(A) receptor antagonist, but not saclofen, a GABA(B) receptor antagonist, blocked the stimulatory effect of GABA on serum GTH-II. Elevation of brain and pituitary GABA levels with the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG), decreased hypothalamic and pituitary dopamine (DA) turnover rates, indicating that GABA may stimulate GTH-II release in the goldfish by decreasing dopaminergic inhibition of GTH-II release. The release of GTH-II stimulated by muscimol and GVG was potentiated by pharmacological agents that decrease inhibitory dopaminergic tone, indicating that DA may also inhibit GABA-stimulated GTH-II release. Based on the linear 24-h accumulation of GABA in brain and pituitary after GVG injection, implantation of testosterone, estradiol, or progesterone, previously shown to regulate the serum GTH-II release response to gonadotropin-releasing hormone and GABA, was also found to modulate GABA synthesis in the brain and pituitary. These results suggest that in the goldfish, GABA stimulates GTH-II release predominantly via a GABA(A) type receptor, and the stimulatory action of GABA can be modulated by DA and sex steroids.