Behavioral effects of benzodiazepine ligands in non-dependent, diazepam-dependent and diazepam-withdrawn baboons

Christine A. Sannerud, Michael Alien, James M. Cook, Roland R. Griffiths

Research output: Contribution to journalArticlepeer-review

Abstract

Acute i.m. injections of benzodiazepine receptor ligands were administered to baboons before 1-h observational sessions. The agonist midazolam produced sedative effects, the antagonist flumazenil produced no behavioral effects, the inverse agonist FG7142 produced tremor and the inverse agonist 3-carboethoxy-β-carboline hydrochloride (βCCE) produced tremor, vomiting, jerks and seizures. Co-administration of these drugs (midazolam + βCCE, midazolam + flumazenil or flumazenil + βCCE) produced a mutual antagonism of these effects. Compared to the non-dependent condition, in the diazepam-dependent condition (baboons maintained on 20 mg/kg per day diazepam) and withdrawn condition (dependent baboons tested during withdrawal), midazolam produced decreased sedative effects, flumazenil produced increased effects (i.e., tremor, vomiting and jerks), and βCCE produced increased frequency of seizures. Taken together, these data suggest that (1) benzodiazepine receptor ligands lie on a continuum of behavioral activity, and (2) chronic diazepam administration alters the behavioral effects of these benzodiazepine ligands, producing a shift in the direction of the inverse agonist.

Original languageEnglish (US)
Pages (from-to)159-169
Number of pages11
JournalEuropean Journal of Pharmacology
Volume202
Issue number2
DOIs
StatePublished - Sep 17 1991

Keywords

  • (Baboon)
  • 3-carboethoxy-β-carboline hydrochloride
  • Cβ-CCE
  • Dependence
  • Diazepam
  • FG7142
  • Flumazenil
  • GABA
  • Midazolam
  • γ-aminobutyric acid

ASJC Scopus subject areas

  • Pharmacology

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