Increased growth hormone secretagogue receptor-1a (GHSR-1a) in hypothalamus during olanzapine treatment in rats

Psychoneuroendocrinology. 2022 Oct;144:105862. doi: 10.1016/j.psyneuen.2022.105862. Epub 2022 Jul 6.


Weight gain is the one of the most important factors which increases global burden of psychiatric disorder. Second-generation antipsychotics, olanzapine (Olz) and valproic acid (Vpa) in particular, are held responsible for weight gain. However, it is still uncertain how these drugs cause this. Thus, the rats selected for the experiment were randomly divided into 3 groups. The 1st group received only 0.5 ml saline solution intraperitoneally (n = 20, control group); the second group was given 200 mg / kg Vpa intraperitoneally (n = 20, Vpa group) and 2 mg / kg Olz was given intraperitoneally to the 3rd group (n = 20, Olz group) between 8 and 10 am for 30 days. We examined serum leptin, adiponectin, resistin, TNF-α, IL-6, ghrelin level and, the amount of ghrelin secreting cells in the stomach and growth hormone secretagogue receptor-1a (GHSR-1a, ghrelin receptor) expression in the hypothalamus. The hypothalamic GHS-1a receptor index was significantly higher in the Olz group compared with the control group and Vpa group (p = 0.036 and p = 0.016 respectively). Ghrelin immune positive cell index in stomach was statistically significantly lower in the Vpa group compared with the control and Olz groups (p = 0.028 and p = 0.013 respectively) There was no difference between the groups in terms of serum leptin, resistin, IL-6 and ghrelin levels. In the Vpa group, a statistically significant increase was found in serum adiponectin level compared with both the control group and the Olz group (p = 0009 and p = 0024 respectively) and, significant decrease was found in serum TNF-α level compared to Olz group (p = 0007). In conclusion, we found that the main cause of weight gain in Olz use was the increase in the number of hypothalamic ghrelin receptors. Investigating the mechanism by which Olz increases the number of ghrelin receptors may help to develop effective treatment strategies in preventing obesity in psychiatric patients.

Keywords: Adipocytokines; GHSR-1a; Ghrelin; Olanzapine; Valproic acid; Weigth gain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / metabolism
  • Animals
  • Ghrelin* / metabolism
  • Ghrelin* / pharmacology
  • Hypothalamus / metabolism
  • Interleukin-6 / metabolism
  • Leptin / metabolism
  • Olanzapine / pharmacology
  • Rats
  • Receptors, Ghrelin* / metabolism
  • Resistin / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Valproic Acid / pharmacology
  • Weight Gain


  • Adiponectin
  • Ghrelin
  • Interleukin-6
  • Leptin
  • Receptors, Ghrelin
  • Resistin
  • Tumor Necrosis Factor-alpha
  • Valproic Acid
  • Olanzapine