Hyperphagia and increased meal size are responsible for weight gain in rats treated sub-chronically with olanzapine |
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Authors: | Nima Davoodi Mikhail Kalinichev Sergei A Korneev and Peter G Clifton |
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Institution: | (1) Department of Psychology, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK;(2) Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline PLC, New Frontiers Science Park, Harlow, Essex, CM19 5AW, UK;(3) Sussex Centre for Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK |
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Abstract: | 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. |
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Keywords: | Antipsychotic Appetite Hyperphagia Hypothalamus Meal size mRNA Olanzapine Pair feeding Rat Weight gain |
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