Tail suspension test does not detect antidepressant-like properties of atypical antipsychotics

The purpose of this study was to investigate the potency of atypical antipsychotics (clozapine, olanzapine, amisulpride, quetiapine, aripiprazole, risperidone) to reduce immobility time and to increase the fighting power, and the number of fights in an automated version of the tail suspension test in C57BL/6J mice. Antidepressant drugs, citalopram and imipramine were tested for comparison. Olanzapine (0.125-5 mg/kg), amisulpride (0.5-2 mg/kg), quetiapine (0.25-2 mg/kg), aripiprazole (0.25-1 mg/kg), and risperidone (0.005-0.05 mg/kg) did not produce any antidepressant-like effect. Only clozapine (0.156-2.5 mg/kg), administered at a dose of 0.312 mg/kg, significantly increased the number of fight episodes. As expected, citalopram (20-40 mg/kg) and imipramine (10-30 mg/kg) dose dependently produced antidepressant-like activity in the same procedure. The effect of antipsychotics on spontaneous locomotor activity and MK-801-induced or d-amphetamine-induced hyperactivity, were also tested in CD-1 mice to confirm the active doses of these drugs in tests commonly used to predict antipsychotic-like activity. Careful screening of potential antipsychotics for their antidepressant effects is considered to be an important part of modern drug development. Our data suggest that the tail suspension test in mice may be relatively insensitive to antidepressant-like activity of atypical antipsychotic drugs with antidepressant properties confirmed by clinical trials.