TY - JOUR
T1 - Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats
AU - Fowler, S. W.
AU - Ramsey, A. K.
AU - Walker, J. M.
AU - Serfozo, P.
AU - Olive, M. F.
AU - Schachtman, T. R.
AU - Simonyi, A.
N1 - Funding Information:
This study was partially supported by 1R21 AT 003859 and 1R01 DA024355 from NIH. We thank Drs. Dennis K. Miller and Kelli R. Rodvelt for generously providing the opportunity and training to use the Med Associates Open-Field Test apparatus.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - Conditioned taste aversion
KW - Inhibitory avoidance
KW - Metabotropic glutamate receptor 5
KW - NMDA receptor
KW - Open-field
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U2 - 10.1016/j.nlm.2010.11.009
DO - 10.1016/j.nlm.2010.11.009
M3 - Article
C2 - 21093598
AN - SCOPUS:78651237783
SN - 1074-7427
VL - 95
SP - 73
EP - 79
JO - Neurobiology of Learning and Memory
JF - Neurobiology of Learning and Memory
IS - 1
ER -