Chronic administration of quetiapine alleviates the anxiety-like behavioural changes induced by a neurotoxic regimen of dl-amphetamine in rats

We have demonstrated that the atypical antipsychotic drugs prevent cell death in PC12 cells induced by various cytotoxins and have protective effects on methamphetamine-induced neurotoxcity in rats. The present study was designed to examine the possible effects of chronic administration of quetiapine, an atypical antipsychotic drug, on the anxiety-like behavioural consequences of a neurotoxic regimen of dl-amphetamine. Rats were treated with quetiapine (10 mg/kg/day; i.p.) for 33 days. During days 15-19 of this period, the animals were given dl-amphetamine (20 mg/kg/day; s.c.) I h after the administration of quetiapine. The repeated administration of dl-amphetamine resulted in a decrease of tyrosine hydroxylase (TH) immunostaining in the caudate putamen, hyperthermia, and anxiety-like behavioural changes. The behavioural changes were indicated by a significant increase in the time spent in the light box in the light/dark box test, an increase in the ratios of ambulation distance inside the inner circle over the total ambulation distance and rearings inside the inner circle over the total rearings in the open field test, and an increase in the time spent in open arms in the elevated plus-maze test. Chronic administration of quetiapine significantly attenuated the dl-amphetamine-induced hyperthermia. and the anxiety-like behavioural changes in the light/dark box and in the open field tests. These results suggest that quetiapine can normalize the dl-amphetamine-induced anxiety-like behavioural changes, and might be helpful in the treatment for amphetamine-induced emotional changes. (c) 2004 Elsevier B.V. All rights reserved.