The effects of chronic administration of quetiapine on the phencyclidine-induced reference memory impairment and...

Quetiapine, a new atypical antipsychotic drug, effectively alleviates positive and negative symptoms, as well as cognitive impairment that may be caused by neurodegeneration, in schizophrenia patients. Earlier in vivo and in vitro studies have demonstrated that quetiapine may be a neuroprotectant. The present study was designed to examine the beneficial effects of quetiapine on the possible cognitive impairment and changes of brain apoptotic regulation proteins induced by phencyclidine (PCP) in rats. Rats were treated with quetiapine (10 mg/kg/day; intraperitoneal (i.p.)) or vehicle for 16 days. On day 14, 1 h after the administration of quetiapine, the rats were given PCP (50 mg/kg; subcutaneous (s.c.)) or vehicle. Then quetiapine was administrated for an additional 2 days. One day after the last quetiapine injection (3 days after the PCP injection), the rats were trained on a spatial memory task in a radial arm maze. After the behavioural test, the rats were decapitated for Western blot analysis. PCP induced reference memory impairment, and a decrease of the ratio of an anti-apoptotic Bcl-2 family member (Bcl-XL) to a pro-apoptotic analogue (Bax) in the posterior cingulate cortex. Chronic administration of quetiapine counteracted the PCP-induced reference memory impairment and decrease of Bcl-XL/Bax ratio in the posterior cingulate cortex. These results suggest that quetiapine may have ameliorating effects on the cognitive impairment and brain apoptotic processes induced by PCP.