Assessment of zolpidem and Cl‐966 for anxiolytic and anxiogenic properties by using the discrimination of pentylenetetrazole by rats

M. W. Emmett‐Oglesby, S. L. Abdel‐Malek

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

This experiment determined if two novel compounds, zolpidem and CI‐966, would show anxiogenic or anxiolytic activity in an animal model of anxiety based upon the discrimination of pentylentetrazole (PTZ). Rats were trained to detect the anxiogenic drug PTZ, 20 mg/kg, and tested with zolpidem (an agonist at omega [benzodiazepine] receptors) and CI‐966 (a GABA‐uptake inhibitor). Zolpidem did not substitute for PTZ. This drug blocked the PTZ stimulus in a dose‐related manner (0.32–5.0 mg/kg), although only partial blockade was obtained even at the highest dose that could be tested. These data suggest that zolpidem may have weak efficacy as an anxiolytic drug. CI‐966 partially substituted for PTZ at 3 to 6 hr post injection of doses of 16.0 and 32.0 mg/kg. Lower doses of CI‐966 produced a slight, but non‐significant, blockade of the PTZ stimulus, which appeared to be additive with the blocking effects of diazepam upon this discrimination. Because CI‐966 has been shown to block PTZ seizures in mice, the present data suggest that the discriminative stimulus produced by PTZ is not related to its ability to produce convulsions. The partial substitution of CI‐966 given in high doses is consistent with clinical reports that this compound may produce anxiogenic effects.

Original languageEnglish
Pages (from-to)243-252
Number of pages10
JournalDrug Development Research
Volume21
Issue number3
DOIs
StatePublished - 1990

Keywords

  • CI‐966
  • anxiety
  • anxiolytic
  • drug discrimination
  • pentylenetetrazole
  • zolpidem

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