Abstract
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 (icv) injection of different doses of the GABA A receptor agonist muscimol (0.25, 0.5, and 1 μg/rat) increased %OAE and %OAT and decreased %CAT in rats dose-dependently. The higher response was obtained with 1 μg/rat of the drug. Neither icv (0.05, 0.1, and 0.2 μg/rat) nor intraperitoneal (ip) (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 μg/rat icv) increased %OAE and %OAT and decreased %CAT in the animals. The response induced by injection of muscimol (0.5 μg/rat icv) or administration of CGP35348 (10 μg/rat icv) was reduced by icv (1, 2, and 4 μg/rat) or ip (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 ip administration of bicuculline. Ip but not icv 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.
Published Version
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