The sex-dependent impact of chronic clozapine and haloperidol treatment on characteristics of the metabolic syndrome in a rat model

Pharmacopsychiatry. 2013 Jan;46(1):1-9. doi: 10.1055/s-0032-1321907. Epub 2012 Aug 22.

Abstract

Introduction: An increased risk for metabolic syndrome has been described for patients with psychotic disorders. Antipsychotic drugs possibly contribute to metabolic changes.

Methods: Haloperidol or clozapine was orally fed to male and female Sprague Dawley rats for 12 weeks, and body weight gain, food and water intake were measured. The serum levels of fasting glucose, HbA1c, triglycerides, cholesterol, HDL and LDL, insulin, leptin, adiponectin and ghrelin were determined. Gonadal and perirenal fat pads were removed and weighed.

Results: We found increased body weight in the male clozapine group, but decreased ones in the male haloperidol group. Clozapine-treated male and female animals had higher fasting glucose, adiponectin, leptin, ghrelin, cholesterol, HDL and LDL levels, whereas haloperidol caused increased levels of insulin and decreased values of HbA1c, cholesterol, HDL and LDL.

Conclusion: Both antipsychotic drugs cause sex-dependent metabolic changes, which are risk factors for the metabolic syndrome, be it hyperinsulinemia under haloperidol treatment or hyperglycemia, hyperleptinemia and hyperlipidemia under clozapine.

MeSH terms

  • Adiposity / drug effects
  • Animals
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / pharmacology*
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Clozapine / blood
  • Clozapine / pharmacology*
  • Drinking / drug effects
  • Eating / drug effects
  • Female
  • Haloperidol / blood
  • Haloperidol / pharmacology*
  • Hormones / blood
  • Insulin / metabolism
  • Lipids / blood
  • Male
  • Metabolic Syndrome / metabolism*
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics
  • Weight Gain / drug effects

Substances

  • Antipsychotic Agents
  • Blood Glucose
  • Hormones
  • Insulin
  • Lipids
  • Clozapine
  • Haloperidol