Short- and long-term effects of antipsychotic drug treatment on weight gain and H1 receptor expression

Han, Mei, Deng, Chao, Burne, Thomas H.J., Newell, Kelly A. and Huang, Xu-Feng F. (2008) Short- and long-term effects of antipsychotic drug treatment on weight gain and H1 receptor expression. Psychoneuroendocrinology, 33 5: 569-580. doi:10.1016/j.psyneuen.2008.01.018

Author Han, Mei
Deng, Chao
Burne, Thomas H.J.
Newell, Kelly A.
Huang, Xu-Feng F.
Title Short- and long-term effects of antipsychotic drug treatment on weight gain and H1 receptor expression
Journal name Psychoneuroendocrinology   Check publisher's open access policy
ISSN 0306-4530
Publication date 2008-03-20
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.psyneuen.2008.01.018
Open Access Status Not yet assessed
Volume 33
Issue 5
Start page 569
End page 580
Total pages 12
Editor Kalin Ned H.
Dantzer, Robert
Place of publication United Kingdom
Publisher Pergamon
Language eng
Subject C1
110999 Neurosciences not elsewhere classified
920111 Nervous System and Disorders
Abstract The present study investigated body weight gain, food intake, open-field activity and brain histamine H1 receptor mRNA and protein expression in rats treated with three types of antipsychotics. Rats were divided into eight groups and treated with aripiprazole (2.25 mg/kg/day), olanzapine (1.5 mg/kg/day), haloperidol (0.3 mg/kg/day) or vehicle (as control) for 1 or 12 weeks. Administration of olanzapine for 1 week led to a threefold increase in body weight gain and a 35% increase in fat deposits compared to controls (p < 0.05). In the 12-week olanzapine treatment group, accumulative food intake was significantly higher in the first 7 weeks of treatment compared to controls (p < 0.018), while body weight gain was significantly greater in the first 8 weeks compared to controls (p < 0.045). Using in situ hybridization, we found that olanzapine treatment, but not aripiprazole or haloperidol treatment, significantly reduced H1 receptor mRNA expression in the arcuate hypothalamic nucleus (Arc: -18%, p = 0.006, 1 week; -20%, p = 0.008, 12 weeks) and ventromedial hypothalamic nucleus (VMH: -22%, p = 0.006, 1 week; -19%, p = 0.042, 12 weeks) compared to controls. The quantitative autoradiography data showed a reduction in VMH H1 receptor binding density after 1 (-12%, p = 0.040) and 12 (-10%, p = 0.094) weeks of olanzapine treatment. There were significant negative correlations between the levels of H1 receptor mRNA expression, and body weight gain and energy efficiency in the Arc and VMH after 1- and 12-week antipsychotic treatments in all groups. In addition, H1 receptor mRNA expression in the Arc showed a significant negative correlation with food intake and fat mass in all groups. Furthermore, there were negative correlations between H1 receptor binding density in the VMH and total fat mass and body weight gain after 1 week of antipsychotic treatment. The present study suggests that downregulated VMH and Arc H1 receptor expression may be a key factor contributing to olanzapine-induced obesity. (C) 2008 Elsevier Ltd. All rights reserved.
Keyword Endocrinology & Metabolism
Endocrinology & Metabolism
Neurosciences & Neurology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 65 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 03 Apr 2009, 03:00:39 EST by Debra McMurtrie on behalf of Queensland Brain Institute