Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats

Psychopharmacology (Berl). 2006 Sep;187(4):397-404. doi: 10.1007/s00213-006-0440-1. Epub 2006 Jun 20.


Rationale: Metabotropic glutamate receptors (mGluRs) were reported to regulate various behavioral effects of addictive drugs.

Objective: The present study evaluated the role of group I mGluRs in the progressive augmentation ("sensitization") of the behavioral effects observed after repeated, intermittent cocaine exposure.

Materials and methods: After habituation to handling and baseline activity measurement (days 1-2), rats received eight injections of cocaine (10 mg/kg) or saline on days 3-6, 8-11, and then, were tested twice with acute saline and cocaine given in a counterbalanced manner on days 13 and 15. Before the test sessions, subjects were pretreated with mGluR1 antagonist EMQMCM (JNJ16567083, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine).

Results: Pretreatment with EMQMCM (2.5-10 mg/kg) but not MTEP (2.5-10 mg/kg) significantly reduced expression of the sensitized ambulatory motor activity of the cocaine-experienced animals acutely challenged with cocaine. Both EMQMCM and MTEP significantly reduced vertical motor activity across all cocaine/saline treatment conditions.

Conclusions: These findings indicate that the expression of behavioral sensitization to cocaine-induced stimulation of locomotor activity may be modulated by group I mGluR antagonists (mGluR1 rather than mGluR5), but these effects occur at the dose levels that attenuate vertical activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Central Nervous System Stimulants / pharmacology*
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / metabolism
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Motor Activity / drug effects*
  • Pyridines / pharmacology
  • Quinolines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / metabolism
  • Thiazoles / pharmacology
  • Time Factors


  • (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate
  • 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine
  • Central Nervous System Stimulants
  • Excitatory Amino Acid Antagonists
  • Grm5 protein, rat
  • Pyridines
  • Quinolines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Thiazoles
  • metabotropic glutamate receptor type 1
  • Cocaine