The effects of the mGluR5 antagonist MPEP and the mGluR2/3 antagonist LY341495 on rats' performance in the 5-choice serial reaction time task

Neuropharmacology. 2007 Mar;52(3):863-72. doi: 10.1016/j.neuropharm.2006.10.003. Epub 2006 Nov 28.


Schizophrenia is characterized by attentional deficits possibly associated with glutamate dysfunction. The role of postsynaptic metabotropic glutamate 5 receptors (mGluR5) or presynaptic inhibitory mGluR2/3 on attention is currently unknown. We investigated the effects of the mGluR5 antagonist MPEP (2-methyl-6[phenylethynyl]-pyridine) and the mGluR2/3 antagonist LY341495 on attention in the 5-choice serial reaction time task (5CSRTT), as well as on food intake to evaluate their effects on food motivation. The effects of pre-feeding and the muscle relaxant curare were examined to characterize the effects of alterations in the motivation or ability to perform the task, respectively. MPEP had no effect on accuracy but overall decreased performance in the 5CSRTT, including decreased speed of responding and decreased premature responses. LY341495 had no significant effect on rats' performance in the 5CSRTT. LY341495 decreased food intake in the home cage to a greater extent than MPEP. Curare decreased the speed of correct responding, reflecting motor impairment. Free feeding decreased overall performance, number of trials completed and number of head entries into the feeder, reflecting decreased motivation to perform the task. Thus, blockade of mGluR5, but not mGluR2/3, decreased overall responding without affecting accuracy in the 5CSRTT.

Publication types

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

MeSH terms

  • Amino Acids / pharmacology*
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Choice Behavior / drug effects*
  • Curare / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Nicotinic Antagonists / pharmacology
  • Pyridines / pharmacology*
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects*
  • Xanthenes / pharmacology*


  • Amino Acids
  • Excitatory Amino Acid Antagonists
  • LY 341495
  • Nicotinic Antagonists
  • Pyridines
  • Xanthenes
  • 6-methyl-2-(phenylethynyl)pyridine
  • Curare