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.
Department of Experimental Biology and Medicine, Rudjer Boskovic Institute Bijenicka, Zagreb, Yugoslavia.
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Manev
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Pericić
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D003000:Clonidine; D003345:Corticosterone; D003907:Dexamethasone; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid; C017985:progabide