Progabide, a GABA mimetic drug, stimulates the secretion of plasma corticosterone in rats

The gamma-aminobutyric acid (GABA) receptor agonist, progabide, was administered intraperitoneally to male Wistar rats. Doses of 50, 100 and 200 mg/kg increased the plasma corticosterone levels by 244, 365 and 476% respectively. Ten mg/kg was ineffective. The enhancement of plasma corticosterone level induced by 200 mg/kg of progabide lasted for 2 hours. The pretreatment of rats with the synthetic corticoid dexamethasone (3 days, 1 mg/kg daily) lowered the plasma corticosterone concentration and abolished its rise induced by progabide. Alpha-2 adrenergic agonist, clonidine (1 mg/kg), elevated the resting plasma corticosterone level but diminished the progabide-induced increase of plasma corticosterone concentration. GABA-A receptor blocking agent, picrotoxin (3 mg/kg), as well as ether stress increased the basal corticosterone level, but both treatments were without effect in progabide-pretreated rats. The results suggest that progabide stimulates the secretion of corticosterone by acting at a site different than the adrenal cortex. It appears that GABA-agonistic activity of progabide is not directly responsible for this effect.