mGlu1 receptor blockade attenuates cue- and nicotine-induced reinstatement of extinguished nicotine self-administration behavior in rats

Neuropharmacology. 2007 Feb;52(2):263-9. doi: 10.1016/j.neuropharm.2006.07.023. Epub 2006 Sep 11.


Glutamatergic neurotransmission is believed to be critically involved in the acquisition and maintenance of drug addiction. The present study evaluated the role of metabotropic glutamate (mGlu) 1 receptors in the reinstatement of nicotine-seeking behavior. Rats were trained to nose-poke to receive response-contingent intravenous infusions of nicotine (0.01 mg/kg/infusion, free base). Following the subsequent extinction phase, reinstatement tests were conducted in animals that were exposed either to response-contingent presentations of the nicotine-associated discrete light cues or to non-contingent nicotine priming injection (0.3mg/kg, s.c., salt) just prior to the test session. In a separate experiment, rats were subjected to the nearly identical response-reinstatement procedure but operant responding was established using food pellets instead of nicotine infusions. Pretreatment with the mGlu1 receptor antagonist EMQMCM (JNJ16567083, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) significantly inhibited cue-induced reinstatement of nicotine-seeking behavior (5 and 10, but not 2.5 mg/kg). EMQMCM (5 mg/kg) also prevented nicotine priming-induced reinstatement of nicotine-seeking behavior. At the highest tested dose only (10 mg/kg), EMQMCM attenuated cue-induced reinstatement of food-seeking behavior. Taken together with the previous reports, the present findings further suggest that blockade of mGlu1 receptors may be beneficial for preventing relapse to tobacco smoking in nicotine-dependent individuals.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal
  • Conditioning, Operant / drug effects
  • Cues*
  • Dose-Response Relationship, Drug
  • Extinction, Psychological / drug effects*
  • Feeding Behavior / drug effects
  • Food
  • Male
  • Nicotine / administration & dosage*
  • Nicotinic Agonists / administration & dosage*
  • Quinolines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Reinforcement, Psychology*
  • Self Administration / methods


  • (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate
  • Nicotinic Agonists
  • Quinolines
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Nicotine