Olanzapine treatment decreases the density of muscarinic M2 receptors in the dorsal vagal complex of rats

Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):915-20. doi: 10.1016/j.pnpbp.2007.02.009. Epub 2007 Feb 20.

Abstract

In this study, we investigated the effects of antipsychotic drugs, olanzapine and haloperidol, on the density of the muscarinic M2 receptors in the dorsal vagal complex (DVC) and hypoglossal nucleus (HN). Female Sprague Dawley rats were treated with olanzapine, haloperidol or vehicle (control) for 1 (short-term) or 12 weeks (long-term). Quantitative autoradiography was used to investigate the M2 receptor density in the DVC and HN using a muscarinic antagonist [(3)H] AF-DX384. Olanzapine, but not haloperidol, treatment induced a significant decrease in the binding density of M2 receptors in the DVC compared to control groups. Although the HN showed a higher density of [(3)H] AF-DX384 binding than the DVC, treatment with both olanzapine and haloperidol did not induce any significant changes in [(3)H] AF-DX384 binding in the HN. These results suggest that olanzapine-induced body weight gain may be associated with functional changes in the muscarinic neurotransmission in the DVC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Autoradiography / methods
  • Benzodiazepines / pharmacology
  • Binding, Competitive / drug effects
  • Female
  • Gene Expression Regulation / drug effects*
  • Medulla Oblongata / drug effects*
  • Olanzapine
  • Parasympatholytics / pharmacokinetics
  • Pirenzepine / analogs & derivatives
  • Pirenzepine / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Muscarinic M2 / metabolism*
  • Tritium / pharmacokinetics
  • Weight Gain / drug effects

Substances

  • Antipsychotic Agents
  • Parasympatholytics
  • Receptor, Muscarinic M2
  • Tritium
  • AFDX 384
  • Benzodiazepines
  • Pirenzepine
  • Olanzapine