Time-dependent ghrelinergic signaling and hyperphagia induced by olanzapine
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
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