gamma-Aminobutyric acid receptor-mediated regulation of periventricular-hypophysial dopaminergic neurons: possible role in mediating stress- and 5-hydroxytryptamine-induced decreases in neuronal activity.

The present study examined the effects of gamma-aminobutyric acid (GABA) agonists and antagonists on basal periventricular-hypophysial dopaminergic (PHDA) neuronal activity with a focus on the role of endogenous GABA in mediating 5-hydroxytryptamine- and stress-induced decreases in PHDA neuronal activity. PHDA neuronal activity was estimated by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in terminals of these neurons in the intermediate lobe of the pituitary. Plasma concentrations of alpha-melanocyte-stimulating hormone (alpha MSH) also were determined to provide a further index of PHDA neuronal activity. Administration of the GABAB agonist baclofen, but not the GABAA agonist isoguvacine, produced dose- and time-related decreases in intermediate lobe DOPAC concentrations and corresponding increases in plasma alpha MSH concentrations. Administration of either the GABAA antagonist SR-95,531 [2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)-pyridazinium bromide] or GABAB antagonists 2-hydroxysaclofen and CGP-35,348 [P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid; SR-95-531 did not alter basal intermediate lobe DOPAC concentrations or plasma alpha MSH concentrations per se, indicating that endogenous GABA does not tonically inhibit PHDA neuronal activity or alpha MSH secretion. 2-Hydroxysaclofen and CGP-35,348 did, however, reverse the baclofen-induced decrease in intermediate lobe DOPAC concentrations and increase in plasma alpha MSH concentrations. In a similar fashion, 2-hydroxysaclofen blocked the inhibitory effects of stress and the 5-hydroxytryptamine2/1c receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane] on PHDA neuronal activity. These results indicate that GABAB and not GABAA receptor activation inhibits basal PHDA neuronal activity, and that GABAB receptor activation mediates the inhibitory effects of 5-hydroxytryptamine and stress on PHDA neurons.