Hyperphagia and increased meal size are responsible for weight gain in rats treated sub-chronically with olanzapine

Davoodi, Nima, Kalinichev, Mikhail, Korneev, Sergei A. and Clifton, Peter G. (2009) Hyperphagia and increased meal size are responsible for weight gain in rats treated sub-chronically with olanzapine. Psychopharmacology, 203 (4). pp. 693-702. ISSN 0033-3158

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Rationale: Atypical antipsychotic-induced weight gain is a significant impediment in the treatment of schizophrenia. Objectives: In a putative model of antipsychotic drug-induced weight gain, we investigated the effects of sub-chronic olanzapine on body weight, meal patterns, the expression of genes encoding for hypothalamic feeding-related neuropeptides and the contribution of hyperphagia to olanzapine-induced weight gain in rats. Materials and methods: In experiment 1, female rats received either olanzapine (1 mg/kg, p.o.) or vehicle, twice daily for 7 days, while meal patterns were recorded. At the end of the treatment regimen, we measured the levels of hypothalamic messenger RNAs (mRNAs) encoding neuropeptide-Y (NPY), hypocretin/orexin (HCRT), melanin concentrating hormone and pro-opiomelanocortin. NPY and HCRT mRNA levels were also assessed in a separate cohort of female rats treated acutely with olanzapine (1 mg/kg, p.o.). In experiment 2, we investigated the effect of a pair-feeding paradigm on sub-chronic (1 mg/kg, p.o.) olanzapine-induced weight gain. Results: In experiment 1, sub-chronic olanzapine increased body weight, food intake and meal size. Hypothalamic neuropeptide mRNA levels were unchanged after both acute and sub-chronic olanzapine treatment. In experiment 2, the restriction of food intake to the level of vehicle-treated controls abolished the sub-chronic olanzapine-induced increase in body weight. Conclusions: Hyperphagia mediated by drug-induced impairments in satiety (as evidenced by increased meal size) is a key requirement for olanzapine-induced weight gain in this paradigm. However, olanzapine-induced hyperphagia and weight gain may not be mediated via alterations in the expression of the feeding-related hypothalamic neuropeptides examined in this study.

Item Type: Article
Schools and Departments: School of Psychology > Psychology
Depositing User: Nima Davoodi
Date Deposited: 06 Feb 2012 15:38
Last Modified: 14 Mar 2012 15:36
URI: http://sro.sussex.ac.uk/id/eprint/13692
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