Skip to main content
placeholder image

Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment

Journal Article


Download full-text (Open Access)

Abstract


  • Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (−45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (−51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.

Publication Date


  • 2014

Citation


  • Lian, J., Huang, X., Pai, N. & Deng, C. (2014). Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment. PLoS One, 9 (8), e104160-1-e104160-11.

Scopus Eid


  • 2-s2.0-84905455350

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3263&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2245

Has Global Citation Frequency


Start Page


  • e104160-1

End Page


  • e104160-11

Volume


  • 9

Issue


  • 8

Place Of Publication


  • United States

Abstract


  • Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (−45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (−51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.

Publication Date


  • 2014

Citation


  • Lian, J., Huang, X., Pai, N. & Deng, C. (2014). Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment. PLoS One, 9 (8), e104160-1-e104160-11.

Scopus Eid


  • 2-s2.0-84905455350

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3263&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2245

Has Global Citation Frequency


Start Page


  • e104160-1

End Page


  • e104160-11

Volume


  • 9

Issue


  • 8

Place Of Publication


  • United States