GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures.
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 non-conditioned 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.
Department of Biological Research, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ 08876.
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Corbett
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Fielding
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Cornfeldt
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Dunn
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D007539:Isonicotinic Acids / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012919:Social Behavior; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D014151:Anti-Anxiety Agents; D007539:Isonicotinic Acids; D007555:Isoxazoles; D000625:Aminooxyacetic Acid; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; C015542:gaboxadol; D003975:Diazepam; C015300:isoguvacine