Antidepressant-like and anxiolytic-like actions of the mGlu5 receptor antagonist MTEP, microinjected into lateral septal nuclei of male Wistar rats

Prog Neuropsychopharmacol Biol Psychiatry. 2006 Aug 30;30(6):1129-35. doi: 10.1016/j.pnpbp.2006.04.022. Epub 2006 Jun 8.

Abstract

This study describes the effects of intra-lateral septal infusions of different doses of the mGluR5 antagonist MTEP in the DRL-72 s paradigm and the elevated plus-maze test in rats, two behavioral models known to be sensitive to antidepressant-like and anxiolytic-like drug effects, respectively. Intra-lateral septal infusions of MTEP induced a dose-dependent (5.0 microg/microl, P<0.05; 10.0 microg/microl, P<0.05) increase in reinforced lever presses and a cohesive rightward shift of the inter-response time distribution (5.0 microg/microl, P<0.05; 10.0 microg/microl, P<0.05). These effects are indicative of antidepressant-like actions of the compound. Desipramine, a prototypical antidepressant drug, induced (5.0 microg/microl; P<0.05) similar effects. In the elevated plus-maze test, intra-lateral septal infusions of MTEP (5.0 microg/microl, P<0.05; 10.0 microg/microl, P<0.05) increased the exploration of the open arms without affecting locomotion. This anxiolytic-like effect was similar to that observed with the infusion of the benzodiazepine midazolam (10.0 microg/microl; P<0.05) in the same brain area. It is concluded that intra-lateral septal infusions of the mGlu5 receptor antagonist MTEP produced antidepressant-like actions or anxiolytic-like effects in male rats.

MeSH terms

  • Animals
  • Anti-Anxiety Agents*
  • Antidepressive Agents*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Anxiety / drug therapy
  • Anxiety / psychology
  • Conditioning, Operant / drug effects
  • Desipramine / therapeutic use
  • Dose-Response Relationship, Drug
  • Male
  • Microinjections
  • Midazolam / therapeutic use
  • Motor Activity / drug effects
  • Pyridines / administration & dosage
  • Pyridines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Reinforcement Schedule
  • Septal Nuclei / physiology*
  • Stereotaxic Techniques
  • Thiazoles / administration & dosage
  • Thiazoles / pharmacology*

Substances

  • 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine
  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Grm5 protein, rat
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Thiazoles
  • Midazolam
  • Desipramine