quetiapine-fumarate and 3-nitrotyrosine

The underlying mechanism of atypical antipsychotics in treating cognitive impairment in schizophrenia is unclear. The aim of the present study was to evaluate the effects of quetiapine, an atypical antipsychotic drug, on object recognition memory and hippocampal oxidative stress in a phencyclidine (PCP) rat model of schizophrenia. Rats were treated with chronic quetiapine (10 mg/kg/day, intraperitoneally) for 16 days or acute quetiapine (10 mg/kg/day, intraperitoneally) on day 16. On day 16, 1 h after the administration of quetiapine, the rats were administered PCP (50 mg/kg, subcutaneously). After the last object recognition behavioral test on day 18, the rats were killed for the measurement of hippocampal protein expression of nitrotyrosine, a protein marker of oxidative stress. The results showed that chronic quetiapine significantly attenuated object recognition memory impairment and hippocampal oxidative stress in the PCP-injected rats. These suggest that the attenuating effect of chronic quetiapine on hippocampal oxidative stress may be related to quetiapine's beneficial effects on object recognition memory in PCP rats, and further suggest that neuroprotective mechanisms are involved in chronic quetiapine treatment.

Topics: Animals; Antipsychotic Agents; Female; Hippocampus; Oxidative Stress; Phencyclidine; Quetiapine Fumarate; Rats, Sprague-Dawley; Recognition, Psychology; Schizophrenia; Schizophrenic Psychology; Tyrosine

Previous studies have suggested that quetiapine, an atypical antipsychotic drug, may have beneficial effects on cognitive impairment, and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the effects of quetiapine on memory impairment and pathological changes in an amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mouse model of Alzheimer's disease (AD). Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5mg/(kg day)) for 1, 4, and 7 months in drinking water from the age of 2 months. After 4 and 7 months of continuous quetiapine administration, memory impairment was prevented, and the number of beta-amyloid (Abeta) plaques decreased in the cortex and hippocampus of the transgenic mice. Quetiapine also decreased brain Abeta peptides, beta-secretase activity and expression, and the level of C99 (an APP C-terminal fragment following cleavage by beta-secretase) in the transgenic mice. Furthermore, quetiapine attenuated anxiety-like behavior, up-regulated cerebral Bcl-2 protein, and decreased cerebral nitrotyrosine in the transgenic mice. These findings suggest that quetiapine can alleviate cognitive impairment and pathological changes in an APP/PS1 double transgenic mouse model of AD, and further indicate that quetiapine may have preventive effects in the treatment of AD.

Topics: Aging; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Antipsychotic Agents; Anxiety; Brain; Dibenzothiazepines; Disease Models, Animal; Female; Male; Memory Disorders; Mice; Mice, Transgenic; Plaque, Amyloid; Presenilin-1; Protease Nexins; Proto-Oncogene Proteins c-bcl-2; Quetiapine Fumarate; Receptors, Cell Surface; Tyrosine