The novel mGluR2/3 agonist LY379268 attenuates cue-induced reinstatement of heroin seeking

Neuroreport. 2005 Jun 21;16(9):1013-6. doi: 10.1097/00001756-200506210-00026.


In humans, drug-associated stimuli can provoke heroin relapse during abstinence. In rats, cues paired with heroin self-administration reinstate heroin seeking in a relapse model. The neurobiological mechanisms involved in this reinstatement, however, are largely unknown. Here, we determined the effect of LY379268, an mGluR2/3 agonist that decreases evoked glutamate release, on cue-induced reinstatement of heroin seeking. Systemic injections of LY379268 attenuated reinstatement of heroin seeking induced by exposure to a discrete tone-light cue that was previously paired with heroin infusions during self-administration training. In contrast, LY379268 had no effect on heroin self-administration. Results indicate that glutamate plays an important role in cue-induced reinstatement of heroin seeking and suggest that mGluR2/3 agonists should be considered for the treatment of opiate relapse.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acids / pharmacology*
  • Animals
  • Behavior, Animal
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Conditioning, Operant / drug effects*
  • Cues*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology*
  • Extinction, Psychological / drug effects
  • Heroin / administration & dosage
  • Heroin Dependence / drug therapy*
  • Heroin Dependence / physiopathology
  • Male
  • Narcotics / administration & dosage
  • Rats
  • Rats, Long-Evans
  • Self Administration / methods


  • Amino Acids
  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Agonists
  • LY 379268
  • Narcotics
  • Heroin