The group II metabotropic glutamate receptor agonist, LY379268, inhibits both cocaine- and food-seeking behavior in rats

Psychopharmacology (Berl). 2006 Jun;186(2):143-9. doi: 10.1007/s00213-006-0372-9. Epub 2006 Apr 22.


Rationale: Group II metabotropic glutamate receptor (mGluR2/3) agonists are proposed to serve as potential treatment for addiction.

Objectives: The present study examined the hypothesis that mGluR2/3 agonists exert inhibitory effects on cocaine-induced reinstatement of cocaine-seeking.

Methods: Rats were trained to self-administer either cocaine or control reinforcer (food), then responding on the reinforcer-paired lever was extinguished. Reinstatement of responding was induced by a noncontingent presentation of the self-administered reinforcer (10 mg/kg cocaine, i.p. or 765 mg of food). In one experiment, rats were systemically pretreated with vehicle (Veh) or the mGluR2/3 agonist LY379268 (0.3, 1, or 3 mg/kg, i.p.) 30 min before the reinstatement test session. In a second experiment, Veh or LY379268 (0.05, 0.5, or 5 nmol/side) was microinjected into the nucleus accumbens core (NAc core) 5 min before the reinstatement test session. The effects of LY379268 on cocaine- and food-induced reinstatement on reward seeking were assessed.

Results: Both systemic and intra-NAc core pretreatment with LY379268 inhibited both cocaine- and food-seeking behavior. However, the effect of LY379268 appeared somewhat more effective for cocaine-seeking than food-seeking.

Conclusions: These results support a potential therapeutic role for mGluR2/3 agonists on relapse of cocaine-seeking. However, doses that inhibited cocaine-seeking were only threefold lower than those inhibiting food-seeking, indicating possible unacceptable nonspecific effects. In addition, the NAc core is one site of action where the mGluR2/3 agonists elicit effects on reward-seeking behavior.

Publication types

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

MeSH terms

  • Amino Acids* / administration & dosage
  • Amino Acids* / pharmacology
  • Amino Acids* / therapeutic use
  • Animals
  • Behavior, Animal / drug effects*
  • Bridged Bicyclo Compounds, Heterocyclic* / administration & dosage
  • Bridged Bicyclo Compounds, Heterocyclic* / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Cocaine* / administration & dosage
  • Cocaine* / adverse effects
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / prevention & control*
  • Cocaine-Related Disorders / psychology
  • Dose-Response Relationship, Drug
  • Feeding Behavior / drug effects*
  • Male
  • Microinjections
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / agonists*
  • Self Administration


  • Amino Acids
  • Bridged Bicyclo Compounds, Heterocyclic
  • LY 379268
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Cocaine