INVOLVEMENT OF GABA(B) RECEPTORS IN THE REGULATION OF THE HYPOTHALAMO-PITUITARY-ADRENOCORTICAL (HPA) AXIS IN RATS

Previous experiments have shown that the GABA(B) receptor agonist L-ba clofen given subcutaneously to male rats significantly enhanced plasma concentrations of adrenocorticotropic hormone (ACTH) and the adrenoco rtical hormones corticosterone and aldosterone. The goal of the presen t study was to investigate whether the stimulatory effects on adrenoco rtical steroids elicited by L-baclofen in vivo could be reversed by th e selective GABA(B) antagonist CGP 35 348. One hour before subcutaneou s administration of 3 mg/kg L-baclofen, a dose of 600 mg/kg CGP 35 348 or saline was administered intraperitoneally. The stimulatory effect of L-baclofen on ACTH, corticosterone and aldosterone was significantl y reduced by 60% after pretreatment with CGP 35 348. The GABA(B) antag onist CGP 35 348 by itself had no effect on ACTH or the adrenocortical hormones. These results indicate that GABA(B) receptors are involved in the L-baclofen-induced activation of the HPA axis in rats. In vitro , however, neither L-baclofen nor CGP 35 348 had any effects on cortic osterone and aldosterone release from perifused adrenal cells. These r esults suggest that the participation of GABA(B) receptors in the acti vation of the HPA axis induced by L-baclofen in vivo does not occur at the level of the adrenal gland, and therefore must occur at the level of the pituitary or the brain.