Effects of risperidone treatment on the expression of hypothalamic neuropeptide in appetite regulation in Wistar rats

Brain Res. 2015 Jan 30;1596:146-55. doi: 10.1016/j.brainres.2014.10.070. Epub 2014 Nov 20.

Abstract

Although the use of atypical antipsychotic drugs has been successful in the treatment of schizophrenia, they can cause some complications in the long-term use, including weight gain. Patients using these drugs tend to disrupt treatment primarily due to side effects. The atypical antipsychotic mechanism of action regulates a number of highly disrupted neurotransmitter pathways in the brains of psychotic patients but may also cause impairment of neurohormonal pathways in different brain areas. In this study, we investigated the circulating levels of hypothalamic neurohormones, which are related to appetite regulation; neuropeptide Y (NPY); alpha melanocyte stimulating hormone (α-MSH); cocaine and amphetamine regulated transcript (CART); agouti-related peptide (AgRP); and leptin in male Wistar rats, which were treated with risperidone, a serotonin antagonist, for four weeks. Alterations in the mRNA expression levels of these candidate genes in the hypothalamus were also analyzed. We hypothesized that risperidone treatment might alter both hypothalamic and circulating levels of neuropeptides through serotonergic antagonism, resulting in weight gain. Gene expression studies revealed that the mRNA expression levels of proopiomelanocortin (POMC), AgRP, and NPY decreased as well as their plasma levels, except for NPY. Unexpectedly, CART mRNA levels increased when their plasma levels decreased. Because POMC neurons express the serotonin receptor (5HT2C), the serotonergic antagonism of risperidone on POMC neurons may cause an increase in appetite and thus increase food consumption even in a short-term trial in rats.

Keywords: Atypical antipsychotics; Hypothalamic neuropeptides; Obesity; Risperidone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / genetics
  • Agouti-Related Protein / metabolism
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Appetite / drug effects*
  • Eating / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects*
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • Leptin / blood
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuropeptide Y / genetics
  • Neuropeptide Y / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2C / genetics
  • Receptor, Serotonin, 5-HT2C / metabolism
  • Risperidone / pharmacology*
  • Statistics, Nonparametric
  • alpha-MSH

Substances

  • AGRP protein, rat
  • Agouti-Related Protein
  • Antipsychotic Agents
  • Leptin
  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Neuropeptides
  • Receptor, Serotonin, 5-HT2C
  • cocaine- and amphetamine-regulated transcript protein
  • alpha-MSH
  • Pro-Opiomelanocortin
  • Risperidone