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Abstract
The introduction of atypical antipsychotic drugs offered significant clinical advantages in treatment of schizophrenia. Though,use of some drugs like olanzapine is associated with weight gain (WG) and related metabolic disturbances,collectively known as metabolic syndrome. WG, diabetes and dyslipidemia are major risk factors for cardiovascular disease (CVD). Ziprasidone is known to have minimal effects on WG and those abnormalities. The exact mechanisms by which atypical APDs induce these side effects are unknown.
The present study attempted to establish and validate first an animal model of APD-induced WG that would give better insight into such mechanisms. Three receptor antagonists were employed as probes for this purpose.
Female Wistar rats were chronically given olanzapine (2 mg/kg/day) incorporated into balanced rat food either with or without one of the antagonists. 5-HT2C receptor antagonist SB
242084 (0.3 mg/kg/day), H1 receptor antagonist chlorpheniramine (10mg/kg/day),and mixed H1/5-HT2A/2B/2C antagonist cyproheptadine (10mg/kg/day) were all given once daily i.p. A separate group was given ziprasidone (10 mg/kg/day in diet) to contrast the effects of olanzapine. The outcome measures at the gross metabolic level included food intake and BW (daily recorded) as well as the adiposity index (AI) measured after dissection of animals as the percentage of white adipose tissue (WAT) related to total BW. At the biochemical level, serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR)were measured as markers for glucose homeostasis. In addition, serum leptin and total lipid profile were measured.