Enhanced anxiolytic effect of zacopride enantiomers in diazepam-withdrawn rats.
The effects of a low (0.001 mg/kg) and a high (0.1 mg/kg) dose of the R(+) and S(-) enantiomers of zacopride were investigated in the elevated plus-maze in control-treated and diazepam-withdrawn rats. The rats withdrawn from diazepam were tested 36 h after the last of 28 days of treatment (2 mg/kg per day). The rats withdrawn from diazepam had a significant anxiogenic response, shown by decreases in the percentage of open arm entries and the percentage of time spent on the open arms. The low dose of S(-)-zacopride and both doses of R(+)-zacopride significantly reversed this anxiogenic response. In contrast, in the control-treated rats there were no significant effects on any measure of either isomer at doses of 0.001, 0.1 or 1 mg/kg.
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Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London, UK.
Andrews
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D014151:Anti-Anxiety Agents; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; C055971:zacopride; D003975:Diazepam