Repeated administration of flumazenil does not alter its potency in modifying schedule-controlled behavior in chlordiazepoxide-treated rhesus monkeys

Lisa R Gerak, Charles P France

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8 Citations (Scopus)

Abstract

Previous reports have suggested that the effects of the benzodiazepine antagonist flumazenil diminish over repeated exposure in subjects treated chronically with a benzodiazepine agonist. The current study examined whether the frequency of exposure to flumazenil altered its potency in decreasing rates of responding in monkeys treated with chlordiazepoxide (CDP). Three monkeys responded under u multiple fixed ratio (FR10:FR10) schedule of food presentation and stimulus-shock termination (SST). In untreated monkeys, flumazenil (0.1-3.2 mg/kg) had no effect in either component. After 2 weeks of treatment with 32.0 mg/kg per day of CDP, flumazenil decreased response rates in the food component, with a dose of 3.2 mg/kg decreasing rates to 10% of control; rates in the SST component were not altered by flumazenil. When flumazenil dose-effect curves were redetermined at 28-, 14-, 7-, 4-, 2- or 1- day intervals, there was no further change in the potency of flumazenil in decreasing food-maintained responding. When CDP treatment was terminated, the potency of flumazenil recovered to pre-CDP values within 23 days. These results suggest that dependence develops to CDP, since changes in the potency of flumazenil co-varied with CDP treatment. Moreover, it does not appear as though results from previous reports, that showed a diminished response to frequently-administered flumazenil, can be generalized to all conditions.

Original languageEnglish (US)
Pages (from-to)64-70
Number of pages7
JournalPsychopharmacology
Volume131
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

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Chlordiazepoxide
Flumazenil
Macaca mulatta
Appointments and Schedules
Haplorhini
Benzodiazepines
Food
Shock

Keywords

  • Benzodiazepine
  • Chlordiazepoxide
  • Dependence
  • Flumazenil
  • Rhesus monkeys
  • Schedule-controlled behavior

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Repeated administration of flumazenil does not alter its potency in modifying schedule-controlled behavior in chlordiazepoxide-treated rhesus monkeys",
abstract = "Previous reports have suggested that the effects of the benzodiazepine antagonist flumazenil diminish over repeated exposure in subjects treated chronically with a benzodiazepine agonist. The current study examined whether the frequency of exposure to flumazenil altered its potency in decreasing rates of responding in monkeys treated with chlordiazepoxide (CDP). Three monkeys responded under u multiple fixed ratio (FR10:FR10) schedule of food presentation and stimulus-shock termination (SST). In untreated monkeys, flumazenil (0.1-3.2 mg/kg) had no effect in either component. After 2 weeks of treatment with 32.0 mg/kg per day of CDP, flumazenil decreased response rates in the food component, with a dose of 3.2 mg/kg decreasing rates to 10{\%} of control; rates in the SST component were not altered by flumazenil. When flumazenil dose-effect curves were redetermined at 28-, 14-, 7-, 4-, 2- or 1- day intervals, there was no further change in the potency of flumazenil in decreasing food-maintained responding. When CDP treatment was terminated, the potency of flumazenil recovered to pre-CDP values within 23 days. These results suggest that dependence develops to CDP, since changes in the potency of flumazenil co-varied with CDP treatment. Moreover, it does not appear as though results from previous reports, that showed a diminished response to frequently-administered flumazenil, can be generalized to all conditions.",
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N2 - Previous reports have suggested that the effects of the benzodiazepine antagonist flumazenil diminish over repeated exposure in subjects treated chronically with a benzodiazepine agonist. The current study examined whether the frequency of exposure to flumazenil altered its potency in decreasing rates of responding in monkeys treated with chlordiazepoxide (CDP). Three monkeys responded under u multiple fixed ratio (FR10:FR10) schedule of food presentation and stimulus-shock termination (SST). In untreated monkeys, flumazenil (0.1-3.2 mg/kg) had no effect in either component. After 2 weeks of treatment with 32.0 mg/kg per day of CDP, flumazenil decreased response rates in the food component, with a dose of 3.2 mg/kg decreasing rates to 10% of control; rates in the SST component were not altered by flumazenil. When flumazenil dose-effect curves were redetermined at 28-, 14-, 7-, 4-, 2- or 1- day intervals, there was no further change in the potency of flumazenil in decreasing food-maintained responding. When CDP treatment was terminated, the potency of flumazenil recovered to pre-CDP values within 23 days. These results suggest that dependence develops to CDP, since changes in the potency of flumazenil co-varied with CDP treatment. Moreover, it does not appear as though results from previous reports, that showed a diminished response to frequently-administered flumazenil, can be generalized to all conditions.

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