Catecholamine depletion modulates serum LH levels, GAD67 mRNA, and GABA synthesis in the goldfish

It is established that dopamine inhibits while GABA stimulates LH release in goldfish. In this study, we examine dopaminergic regulation of GABAergic activity in the hypothalamus of early recrudescent female goldfish (Carassius auratus). We utilize a unique technique that permits concomitant quantification and correlation of in vivo GAD65 and GAD67 mRNA with GABA synthesis rate in response to decreased dopamine levels. Catecholamine depletion was achieved by treatment with α-methyl-para-tyrosine methyl ester (αMPT; 240 μg/g body weight), an inhibitor of tyrosine hydroxylase. Endogenous GABA levels were increased by intraperitoneal administration of γ-vinyl GABA (GVG; 300 μg/g body weight), an inhibitor of the GABA catabolic enzyme GABA transaminase. Dual treatment of GVG + αMPT increased serum LH levels 4-fold. However, LH mRNA levels in the pituitary remained stable, suggesting that treatments affected secretion and not synthesis. In the hypothalamus, GABA synthesis rates increased 30% in response to αMPT treatment. This was correlated (r = 0.61; p < 0.05) to increased levels of GAD67 mRNAs but not GAD65 (r = 0.14; p > 0.05). These observations suggest that catecholamines inhibit GABA synthesis in the goldfish hypothalamus through isoform specific regulation of GAD67.