Beta-CCT, a selective BZ-omega1 receptor antagonist, blocks the anti-anxiety but not the amnesic action of chlordiazepoxide in mice.
The aim of this study was to test further the hypothesis that different benzodiazepine (BZ-omega) receptor subtypes may mediate anxiolytic and amnesic effects of BZ agonists, using the selective BZ-omega1 receptor antagonist beta-CCT (beta-carboline-3-carboxylate t-butyl-ester). Experiments were performed in Swiss mice using the elevated plus-maze anxiety test and two learning tasks - passive avoidance and the radial arm maze. In the elevated plus-maze test, beta-CCT (30 mg/kg, i.p.) completely abolished the increase in open-arm entries induced by the BZ chlordiazepoxide (5mg/kg, i.p.). Chlordiazepoxide decreased retention latency in the passive avoidance step-through procedure, and increased the number of errors in the radial arm maze. These effects were not modified by beta-CCT. Except for a slight, albeit significant, amnesic effect in the passive avoidance test, beta-CCT was devoid of intrinsic activity when administered alone. These results are in agreement with previous studies using selective BZ-omega1 agonists, and thus provide further evidence that BZ-omega1 receptors may be involved in the anxiolytic but not in the amnesic effects of BZ agonists.
Belzung
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Laboratoire d'Ethologie et de Pharmacologie du Comportement, UFR Sciences et Techniques, Tours, France. belzung@univ-tours.fr
Le Guisquet
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AM
Griebel
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D000647:Amnesia / Q000139:chemically induced* / Q000523:psychology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice
D014151:Anti-Anxiety Agents; D002243:Carbolines; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D002707:Chlordiazepoxide; C043232:tert-butyl beta-carboline-3-carboxylate