Effects of deletion of gria1 or gria2 genes encoding glutamatergic AMPA-receptor subunits on place preference conditioning in mice

Psychopharmacology (Berl). 2005 Apr;179(1):164-71. doi: 10.1007/s00213-004-2071-8. Epub 2004 Dec 24.


Rationale: The conditioned place preference (CPP) paradigm has been used as a measure of the rewarding effects of a number of stimuli. Critically, this classical conditioning procedure requires the formation of associations between a rewarding stimulus and environmental cues, and the ability of these cues to direct subsequent behaviour.

Objectives: The purpose of the current experiments was to examine the role of glutamatergic transmission via subunit-specific populations of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors in the formation of stimulus--reward associations involving contextual stimuli.

Methods: We investigated the ability of cocaine and food to induce a CPP in mice lacking either the GluR1 or GluR2 subunits of the AMPA receptor [gria1 or gria2 knockout (KO) mice]. In separate experiments, food pellets or cocaine (5--20 mg/kg IP) were paired with one compartment of the CPP apparatus, while no-food or vehicle was paired with an alternative compartment.

Results: Following conditioning, gria1 KOs displayed a significant preference for the food or cocaine-paired compartment, and did not differ from wild-type (WT) controls. However, gria2 knockouts displayed a preference for a cocaine-paired compartment, but not a food-paired compartment, indicating a specific deficit in place preference conditioning to food.

Conclusions: These results obtained using knockout mice indicate that GluR2-containing AMPA receptors may be critical for learning about contextual stimuli relevant to food rewards, but not drug rewards. When the results are considered in relation to our previous findings with gria1 and gria2 knockout mice, they also raise questions about the CPP paradigm representing a model of conditioned reward over a conditioned approach interpretation. However, it would be important to confirm these findings with alternative approaches, should selective ligands become available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology
  • Animals
  • Choice Behavior*
  • Cocaine / administration & dosage
  • Conditioning, Classical*
  • Food
  • Mice
  • Mice, Knockout
  • Receptors, AMPA / genetics
  • Receptors, AMPA / physiology*
  • Reward


  • Receptors, AMPA
  • Cocaine
  • glutamate receptor ionotropic, AMPA 2
  • glutamate receptor ionotropic, AMPA 1