Potentiating mGluR5 function with a positive allosteric modulator enhances adaptive learning

Jian Xu, Yongling Zhu, Stephen Kraniotis, Qionger He, John J. Marshall, Toshihiro Nomura, Shaun R. Stauffer, Craig W. Lindsley, P. Conn Jeffrey, Anis Contractor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Metabotropic glutamate receptor 5 (mGluR5) plays important roles in modulating neural activity and plasticity and has been associated with several neuropathological disorders. Previous work has shown that genetic ablation or pharmacological inhibition of mGluR5 disrupts fear extinction and spatial reversal learning, suggesting that mGluR5 signaling is required for different forms of adaptive learning. Here, we tested whether ADX47273, a selective positive allosteric modulator (PAM) of mGluR5, can enhance adaptive learning in mice. We found that systemic administration of the ADX47273 enhanced reversal learning in the Morris Water Maze, an adaptive task. In addition, we found that ADX47273 had no effect on single-session and multi-session extinction, but administration of ADX47273 after a single retrieval trial enhanced subsequent fear extinction learning. Together these results demonstrate a role for mGluR5 signaling in adaptive learning, and suggest that mGluR5 PAMs represent a viable strategy for treatment of maladaptive learning and for improving behavioral flexibility.

Original languageEnglish (US)
Pages (from-to)438-445
Number of pages8
JournalLearning and Memory
Volume20
Issue number8
DOIs
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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