Beta-CCT, a selective BZ-omega1 receptor antagonist, blocks the anti-anxiety but not the amnesic action of chlordiazepoxide in mice

Behav Pharmacol. 2000 Apr;11(2):125-31. doi: 10.1097/00008877-200004000-00004.

Abstract

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.

MeSH terms

  • Amnesia / chemically induced*
  • Amnesia / psychology
  • Animals
  • Anti-Anxiety Agents / antagonists & inhibitors*
  • Anti-Anxiety Agents / pharmacology*
  • Avoidance Learning / drug effects
  • Brain Chemistry / drug effects
  • Carbolines / pharmacology*
  • Chlordiazepoxide / antagonists & inhibitors*
  • Chlordiazepoxide / pharmacology*
  • Emotions / drug effects
  • GABA Antagonists / pharmacology*
  • GABA-A Receptor Antagonists*
  • Male
  • Memory / drug effects
  • Mice

Substances

  • Anti-Anxiety Agents
  • Carbolines
  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • Chlordiazepoxide
  • tert-butyl beta-carboline-3-carboxylate