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Abstract
The use of atypical antipsychotic drugs (AAPDs) in treatment of schizophrenia has been associated with some adverse effects despite proving their efficacy more than the conventional typical antipsychotics. Weight gain (WG), diabetes, and dyslipidemia are components of metabolic syndrome that pose major cardiovascular threats. The present study aims at establishing an animal model of APD-induced WG valid to provide better insight into the underlying mechanisms.
Female Wistar rats were given olanzapine (OLA) (2 mg/kg/day) single or combined with one of the three receptor antagonists employed as probes; SB 242084, chlorpheniramine (CPA), or cyproheptadine (CYP). They were used as antagonists at 5-HT2C, H1 or H1/5-HT2A/2B/2C receptors in daily doses of 0.3 or 10 mg/kg i.p., respectively. Ziprasidone (ZIP) (10 mg/kg/day) was given for comparison with olanzapine, both incorporated in animal food. Daily food intake (FI) and body weight (BW) were recorded while adiposity was measured after dissection as adiposity index (AI). Serum glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), leptin, and total lipid profile were also measured.
Results showed that OLA single or combined as well as CYP significantly increased cumulative FI (p<0.001) and percentage of total body weight gain (BWG) (p<0.001).