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Time-dependent ghrelinergic signaling and hyperphagia induced by olanzapine

Conference Paper


Abstract


  • Olanzapine is widely used to treat schizophrenia and other mental

    diseases. Interestingly, although increased body weight is evident

    throughout the course of olanzapine treatment, elevated food intake

    only appears in relatively shorter term. Olanzapine can modulate

    ghrelin levels, which may upregulate neuropeptide Y (NPY) secretion

    at hypothalamus. Brain-specific homeobox transcription factor (BSX)

    may also be involved in ghrelin-induced hyperphagia. PURPOSE: To

    investigate the effect of olanzapine on central NPY, BSX and plasma

    ghrelin levels, and their relationship to food intake. METHODS: Rats

    were treated with olanzapine (1mg/kg, orally, 3x/day, n=12/group) or

    vehicle for 1 week, 2 weeks, or 5 weeks. Daily food intake was measured

    on the final day of treatment for further analysis. Postmortem blood

    and brain samples were collected for measurement of plasma ghrelin

    (EIA), hypothalamic NPY protein (EIA) and BSX mRNA levels (real-time

    PCR) (n>5/group). RESULTS: Olanzapine increased daily food intake

    (p<0.001) and ghrelin (p<0.01) after 1-week, but not 2-week (p=0.052

    for ghrelin) or 5-week treatment. Hypothalamic NPY protein increased

    after 1-week (p<0.001) and 2-week (p<0.05), but not 5-week olanzapine

    treatment. Hypothalamic BSX mRNA was increased by 3.6 folds

    (p<0.001) after 1 week, but not after 2 weeks or 5 weeks. NPY positively

    correlated to ghrelin levels after 1 week (r=0.943, p<0.001). Ghrelin

    levels positively correlated to final daily food intake at all times (r=0.702,

    p<0.001) and 1 week post treatment (r=0.801, p<0.01). CONCLUSION:

    Olanzapine increased ghrelin secretion in a time-dependent manner,

    which may explain its time-dependent hyperphagic effect. Olanzapine

    also increased hypothalamic NPY expression time-dependently, possibly

    through elevated plasma ghrelin and hypothalamic BSX levels.

Publication Date


  • 2013

Citation


  • Zhang, Q., He, M., Lian, J., Deng, C. & Huang, X. F. (2013). Time-dependent ghrelinergic signaling and hyperphagia induced by olanzapine. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 48-48). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/897

Start Page


  • 48

End Page


  • 48

Place Of Publication


  • Australia

Abstract


  • Olanzapine is widely used to treat schizophrenia and other mental

    diseases. Interestingly, although increased body weight is evident

    throughout the course of olanzapine treatment, elevated food intake

    only appears in relatively shorter term. Olanzapine can modulate

    ghrelin levels, which may upregulate neuropeptide Y (NPY) secretion

    at hypothalamus. Brain-specific homeobox transcription factor (BSX)

    may also be involved in ghrelin-induced hyperphagia. PURPOSE: To

    investigate the effect of olanzapine on central NPY, BSX and plasma

    ghrelin levels, and their relationship to food intake. METHODS: Rats

    were treated with olanzapine (1mg/kg, orally, 3x/day, n=12/group) or

    vehicle for 1 week, 2 weeks, or 5 weeks. Daily food intake was measured

    on the final day of treatment for further analysis. Postmortem blood

    and brain samples were collected for measurement of plasma ghrelin

    (EIA), hypothalamic NPY protein (EIA) and BSX mRNA levels (real-time

    PCR) (n>5/group). RESULTS: Olanzapine increased daily food intake

    (p<0.001) and ghrelin (p<0.01) after 1-week, but not 2-week (p=0.052

    for ghrelin) or 5-week treatment. Hypothalamic NPY protein increased

    after 1-week (p<0.001) and 2-week (p<0.05), but not 5-week olanzapine

    treatment. Hypothalamic BSX mRNA was increased by 3.6 folds

    (p<0.001) after 1 week, but not after 2 weeks or 5 weeks. NPY positively

    correlated to ghrelin levels after 1 week (r=0.943, p<0.001). Ghrelin

    levels positively correlated to final daily food intake at all times (r=0.702,

    p<0.001) and 1 week post treatment (r=0.801, p<0.01). CONCLUSION:

    Olanzapine increased ghrelin secretion in a time-dependent manner,

    which may explain its time-dependent hyperphagic effect. Olanzapine

    also increased hypothalamic NPY expression time-dependently, possibly

    through elevated plasma ghrelin and hypothalamic BSX levels.

Publication Date


  • 2013

Citation


  • Zhang, Q., He, M., Lian, J., Deng, C. & Huang, X. F. (2013). Time-dependent ghrelinergic signaling and hyperphagia induced by olanzapine. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 48-48). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/897

Start Page


  • 48

End Page


  • 48

Place Of Publication


  • Australia