Effects of mGluR1 Antagonism in the Dorsal Hippocampus on Drug Context-Induced Reinstatement of Cocaine-Seeking Behavior in Rats

Psychopharmacology (Berl). 2010 Jan;208(1):1-11. doi: 10.1007/s00213-009-1700-7. Epub 2009 Oct 22.


Rationale: The functional integrity of the dorsal hippocampus (DH) is necessary for drug context-induced reinstatement of cocaine seeking. However, the neuropharmacological mechanisms of this phenomenon are poorly understood.

Objectives: Given the known significance of group I metabotropic glutamate receptors (mGluRs), including the mGluR1 subtype, in drug-induced behaviors, the present study was designed to evaluate the contribution of mGluR1s in the DH to drug context-induced reinstatement of extinguished cocaine-seeking behavior.

Methods: Sprague-Dawley rats were trained to lever press for unsignaled cocaine infusions in a distinct environmental context (cocaine-paired context) followed by extinction training in a distinctly different environmental context (extinction context). Using a counterbalanced partial within-subjects testing design, rats were re-exposed to the cocaine-paired context or the extinction context while cocaine-seeking behavior (nonreinforced active lever pressing) was assessed. Prior to each test session, rats received bilateral microinfusions of the highly potent mGluR1-selective antagonist JNJ16259685 (0.6, 30, or 120 pg/0.5 microl per hemisphere) or vehicle into the DH or the overlying somatosensory cortex trunk region (SStr; anatomical control).

Results: Intra-DH, but not intra-SStr, JNJ16259685 infusions dose dependently attenuated drug context-induced reinstatement of cocaine seeking relative to vehicle treatment, without attenuating instrumental behavior in the extinction context, general motor activity, or food-reinforced instrumental behavior in control experiments.

Conclusions: Stimulation of mGluR1s in the DH is necessary for incentive motivational and/or memory processes that contribute to drug context-induced cocaine-seeking behavior. These findings indicate that the mGluR1 is an interesting target from an addiction treatment perspective.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Cocaine / administration & dosage*
  • Dose-Response Relationship, Drug
  • Extinction, Psychological / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Quinolines / administration & dosage
  • Quinolines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / metabolism
  • Reinforcement Schedule
  • Self Administration


  • (3,4-dihydro-2H-pyrano(2,3)b-quinolin-7-yl)-(cis-4-methoxycyclohexyl) methanone
  • Quinolines
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Cocaine