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Repeated administration of flumazenil does not alter its potency in modifying schedule-controlled behavior in

L R Gerak1, C P France

  • 1Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70119, USA.

Psychopharmacology
|May 1, 1997
PubMed

Insights

Repeated exposure to chlordiazepoxide (CDP) dependence in monkeys led to changes in flumazenil potency. Flumazenil

Area of Science:

  • Pharmacology
  • Neuroscience
  • Behavioral Science

Background:

  • Benzodiazepine agonists, like chlordiazepoxide (CDP), are commonly prescribed medications.
  • Benzodiazepine antagonists, such as flumazenil, are used to reverse benzodiazepine effects.
  • Previous research indicated diminished flumazenil effects with repeated exposure during chronic benzodiazepine treatment.

Purpose of the Study:

  • To investigate if flumazenil exposure frequency impacts its potency in reducing response rates.
  • To examine flumazenil's effects in monkeys treated with the benzodiazepine agonist chlordiazepoxide (CDP).

Main Methods:

  • Three monkeys were trained on a multiple fixed ratio (FR10:FR10) schedule for food and stimulus-shock termination (SST).
  • Flumazenil dose-effect curves were determined in untreated and CDP-treated monkeys.
  • Flumazenil potency was re-evaluated at various intervals during chronic CDP treatment and after its termination.

Main Results:

  • In untreated monkeys, flumazenil had no significant effect on response rates.
  • After chronic CDP treatment, flumazenil decreased food-maintained responding but not SST responding.
  • Flumazenil potency did not change with varying exposure frequencies during CDP treatment; it recovered after CDP withdrawal.

Conclusions:

  • Dependence on chlordiazepoxide (CDP) was suggested by the observed changes in flumazenil potency.
  • The diminished flumazenil response reported in prior studies may not apply universally.
  • Flumazenil's efficacy is influenced by the presence and duration of benzodiazepine agonist treatment.

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