University of Sussex

File(s) not publicly available

Hyperphagia and increased meal size are responsible for weight gain in rats treated sub-chronically with olanzapine

journal contribution
posted on 2023-06-07, 18:13 authored by Nima Davoodi, Mikhail Kalinichev, Sergei Korneev, Pete CliftonPete Clifton
Rationale: Atypical antipsychotic-induced weight gain is a significant impediment in the treatment of schizophrenia. Objectives: In a putative model of antipsychotic drug-induced weight gain, we investigated the effects of sub-chronic olanzapine on body weight, meal patterns, the expression of genes encoding for hypothalamic feeding-related neuropeptides and the contribution of hyperphagia to olanzapine-induced weight gain in rats. Materials and methods: In experiment 1, female rats received either olanzapine (1 mg/kg, p.o.) or vehicle, twice daily for 7 days, while meal patterns were recorded. At the end of the treatment regimen, we measured the levels of hypothalamic messenger RNAs (mRNAs) encoding neuropeptide-Y (NPY), hypocretin/orexin (HCRT), melanin concentrating hormone and pro-opiomelanocortin. NPY and HCRT mRNA levels were also assessed in a separate cohort of female rats treated acutely with olanzapine (1 mg/kg, p.o.). In experiment 2, we investigated the effect of a pair-feeding paradigm on sub-chronic (1 mg/kg, p.o.) olanzapine-induced weight gain. Results: In experiment 1, sub-chronic olanzapine increased body weight, food intake and meal size. Hypothalamic neuropeptide mRNA levels were unchanged after both acute and sub-chronic olanzapine treatment. In experiment 2, the restriction of food intake to the level of vehicle-treated controls abolished the sub-chronic olanzapine-induced increase in body weight. Conclusions: Hyperphagia mediated by drug-induced impairments in satiety (as evidenced by increased meal size) is a key requirement for olanzapine-induced weight gain in this paradigm. However, olanzapine-induced hyperphagia and weight gain may not be mediated via alterations in the expression of the feeding-related hypothalamic neuropeptides examined in this study.


Publication status

  • Published









Page range




Department affiliated with

  • Psychology Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date


Usage metrics

    University of Sussex (Publications)


    No categories selected