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GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures
Authors:Roy Corbett  Stuart Fielding  Michael Cornfeldt  Robert W. Dunn
Affiliation:(1) Department of Biological Research, Hoechst-Roussel Pharmaceuticals, Inc., Route 202-206 North, P.O. Box 2500, 08876 Somerville, NJ, USA
Abstract:Benzodiazepine (BZD) anxiolytics, through their activation of the BZD-GABA receptor complex, display robust anxiolytic-like effects following systemic administration in both conditioned and non-conditioned behavioral procedures. The present results show that the GABAA agonists muscimol (0.5–1.0 mg/kg), THIP (2.5–10.0 mg/kg), and isoguvacine (25.0 mg/kg) as well as the GABA transaminase (GABA-T) inhibitor AOAA (aminooxyacetic acid; 5.0–20.0 mg/kg) following intraperitoneal administration exert anxiolytic-like activity of similar magnitude to that of diazepam in two nonconditioned procedures, namely the social interaction and the elevated plus maze tests. We have also extended our original findings that the anti-epileptic drug sodium valproate exerts an anxiolytic-like effect in the Geller conflict paradigm, to show this agent's robust activity in the social interaction and elevated plus maze tests following systemic administration (100–400 mg/kg). These results show that GABAergic agents that facilitate GABA transmission are effective following systemic administration in non-conditioned anxiety procedures and may indicate potential therapeutic efficacy in certain anxiety states.
Keywords:GABAmimetics  Benzodiazepines  Anxiolytics  Social interaction  Elevated plus maze  Conflict procedures  Systemic administration
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