The mGluR5 antagonist MTEP dissociates the acquisition of predictive and incentive motivational properties of reward-paired stimuli in mice

Neuropsychopharmacology. 2010 Jul;35(8):1807-17. doi: 10.1038/npp.2010.48. Epub 2010 Apr 7.


An environmental stimulus paired with reward (a conditioned stimulus; CS) can acquire predictive properties that signal reward availability and may also acquire incentive motivational properties that enable the CS to influence appetitive behaviors. The neural mechanisms involved in the acquisition and expression of these CS properties are not fully understood. The metabotropic glutamate receptor, mGluR5, contributes to synaptic plasticity underlying learning and memory processes. We examined the role of mGluR5 in the acquisition and expression of learning that enables a CS to predict reward (goal-tracking) and acquire incentive properties (conditioned reinforcement). Mice were injected with vehicle or the mGluR5 antagonist, MTEP (3 or 10 mg/kg), before each Pavlovian conditioning session in which a stimulus (CS+) was paired with food delivery. Subsequently, in the absence of the primary food reward, we determined whether the CS+ could reinforce a novel instrumental response (conditioned reinforcement) and direct behavior toward the place of reward delivery (goal-tracking). MTEP did not affect performance during the conditioning phase, or the ability of the CS+ to elicit a goal-tracking response. In contrast, 10 mg/kg MTEP given before each conditioning session prevented the subsequent expression of conditioned reinforcement. This dose of MTEP did not affect conditioned reinforcement when administered before the test, in mice that had received vehicle before conditioning sessions. Thus, mGluR5 has a critical role in the acquisition of incentive properties by a CS, but is not required for the expression of incentive learning, or for the CS to acquire predictive properties that signal reward availability.

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Conditioning, Classical / drug effects*
  • Conditioning, Operant / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motivation / drug effects*
  • Pyridines / pharmacology*
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Reward*
  • Thiazoles / pharmacology*


  • 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine
  • Grm5 protein, mouse
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Thiazoles