Effect of low doses of clozapine on behaviour of isolated and group-housed male mice in the elevated plus-maze test

Clozapine is effective over a low and narrow dose range in the treatment of the negative symptoms of schizophrenia. Its efficacy is said to reflect an anxiolytic property of the neuroleptic. This study examined the effects of a low dose range of clozapine (0.1, 0.2 and 0.4 mg/kg) administered to isolated (7 days) and group-housed male mice on their behaviour in the elevated plus-maze. The results using this model of anxiety showed no dose-dependent effect on behaviour after treatment with low doses of clozapine. Some doses (0.1 and 0.4 mg/kg), however, reduced the duration and frequency of open arm entries compared to control-treated mice in the group-housed animals. This might indicate a slight anxiogenic effect. Support for this view is provided by some of the ethological measures, particularly head-dipping (HD). Seven days of isolation did not alter the main anxiety indices in controls. Nevertheless, some measures (e.g. closed entries and duration in the closed arm) were modified by the clozapine treatment (0.2 mg/kg) in a manner suggesting a mild anxiogenic action. The effects of the drug in individually and group-housed male mice were certainly different.