GABA(A) but not GABA(B) receptor stimulation induces antianxiety profile in rats.
The effect of GABA receptor agonists and antagonists on anxiety behavior in rats in the elevated-plus-maze has been investigated. The increase in two parameters of %open arm entries (%OAE) and %time spent in the open arms (%OAT) and decrease in the %time spent in closed arm (%CAT) was considered as antianxiety effects. Intracerebroventricular (i.c.v.) injection of different doses of the GABA(A) receptor agonist muscimol (0.25, 0.5, and 1 microg/rat) increased %OAE and %OAT and decreased %CAT in rats dose-dependently. The higher response was obtained with 1 microg/rat of the drug. Neither icv (0.05, 0.1, and 0.2 microg/rat) nor intraperitoneal (i.p.) (1, 2, and 4 mg/kg) injection of the GABA(B) receptor agonist baclofen altered %OAE, %OAT, and %CAT. However, the GABA(B) receptor antagonist CGP35348 (5, 10, and 30 microg/rat i.c.v.) increased %OAE and %OAT and decreased %CAT in the animals. The response induced by injection of muscimol (0.5 microg/rat i.c.v.) or administration of CGP35348 (10 microg/rat i.c.v.) was reduced by i.c.v. (1, 2, and 4 microg/rat) or i.p. (0.25, 0.5, and 0.75 mg/kg) injection of the GABA(A) receptor antagonist bicuculline, except the effect of CGP35348 on %CAT which was not significantly altered by i.p. administration of bicuculline. Ip but not i.c.v. administration of bicuculline by itself reduced both %OAE and %OAT but did not alter %CAT. None of the drugs altered the locomotor activity of the animals. The current findings support our hypothesis that the anxiolytic effects of GABA(B) antagonist are mediated by autoreceptor blockade-induced release of endogenous GABA, which in turn activates postsynaptic GABA(A) receptors.
Zarrindast
M
M
Department of Pharmacology, Medical School, Tehran University of Medical Sciences, Tehran, Iran.
Rostami
P
P
Sadeghi-Hariri
M
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D009943:Organophosphorus Compounds; D009118:Muscimol; C066430:CGP 35348; D001418:Baclofen; D001640:Bicuculline