Enhanced anxiolytic effect of zacopride enantiomers in diazepam-withdrawn rats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the R(+) and S(-) enantiomers of zacopride were investigated in the elevated plus-maze in control-treated and diazepam-withdrawn rats. The rats withdrawn from diazepam were tested 36 h after the last of 28 days of treatment (2 mg/kg per day). The rats withdrawn from diazepam had a significant anxiogenic response, shown by decreases in the percentage of open arm entries and the percentage of time spent on the open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.