Research Report 1: Olanzapine in Roman rats

Graver, J.C. (2012) Research Report 1: Olanzapine in Roman rats. Master's Thesis / Essay, Biology.

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Abstract

Introduction: Olanzapine is an atypical antipsychotic drug used for treatment of schizophrenic patients. A major side effect of olanzapine is the substantial weight gain. Olanzapine acts predominantly antagonistic on serotonin and dopamine receptors, but also on histamine, muscarinic and α-adrenergic receptors. These multiple action sites make it difficult to elucidate the mechanisms of action of olanzapine. To our knowledge a valid animal model for schizophrenia has not been identified. Therefore this study looked of the effects of olanzapine on body weight, adiposity and insulin sensitivity in Wistar, passive Roman low- (RLA) and proactive Roman high avoidance (RHA) rat. Also effects of OLZ treatment in an active versus a sedentary environment were tested in RLA and RHA rat. Methods: Olanzapine was administered twice daily (2 mg/kg) at the beginning and in the middle of the dark phase, resulting in 4 ml/kg olanzapine per animal per day. On daily basis body weight, food intake and water intake were measured and an intravenous glucose tolerance test was performed to measure insulin and glucose response. Furthermore post mortem analysis was performed. The first project was performed with female Wistar rats. The second and third projects were performed with RLA and RHA rats. Running wheel activity was measured during the second project, whereas cage activity and body temperature were measured in the third project. Results: The first project showed significant increased body weight and insulin levels following olanzapine treatment. During the second project olanzapine treatment of RHA rats showed significantly increased body weight, total fat and visceral fat. Furthermore, running wheel activity was significantly decreased. In RLA rats OLZ only significantly lowered running wheel activity. In the third project cage activity and body temperature were significantly decreased by OLZ treatment in both RLA and RHA rats. Conclusion: Most effects of olanzapine were seen in RHA rats in an active environment, with increased body weight and adiposity. Next to weight gain, only Wistar rats displayed decreased insulin sensitivity. The olanzapine induced decrease of activity was independent of coping style and environment. Also the hypothermic effect of olanzapine was independent of coping style. However, the used animal models in this study did not display all the side effects seen in schizophrenic patients. Therefore, future research should aim at searching a valid animal model which at least displays the side effects of olanzapine on body weight, adiposity and insulin sensitivity.

Item Type:	Thesis (Master's Thesis / Essay)
Degree programme:	Biology
Thesis type:	Master's Thesis / Essay
Language:	English
Date Deposited:	15 Feb 2018 07:55
Last Modified:	15 Feb 2018 07:55
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/11445

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