Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats

S. W. Fowler, A. K. Ramsey, J. M. Walker, P. Serfozo, M. F. Olive, T. R. Schachtman, A. Simonyi

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of learning processes and is important for inhibitory avoidance and conditioned taste aversion learning. MGlu5 receptors are physically connected with NMDA receptors and they interact with, and modulate, the function of one another in several brain regions. The present studies used systemic co-administration of an mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK-801) to characterize the interactions of these receptors in two aversive learning tasks. Male Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10. mg/kg, s.c.), delivered by itself prior to the conditioning trial, did not have any effect on performance in either task 48. h after training. However, CDPPB (at 3. mg/kg) attenuated the MK-801 (0.2. mg/kg, i.p.) induced learning deficit in both tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie the importance of mGlu5 and NMDA receptor interactions in modulating memory processing, and are consistent with findings showing the efficacy of positive allosteric modulators of mGlu5 receptors in reversing the negative effects of NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor gating, or working, spatial and recognition memory.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalNeurobiology of Learning and Memory
Volume95
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Conditioned taste aversion
  • Inhibitory avoidance
  • Metabotropic glutamate receptor 5
  • NMDA receptor
  • Open-field

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Fingerprint Dive into the research topics of 'Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats'. Together they form a unique fingerprint.

  • Cite this

    Fowler, S. W., Ramsey, A. K., Walker, J. M., Serfozo, P., Olive, M. F., Schachtman, T. R., & Simonyi, A. (2011). Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats. Neurobiology of Learning and Memory, 95(1), 73-79. https://doi.org/10.1016/j.nlm.2010.11.009