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Involvement of NMDA receptors in ryanodine receptor expression in dopaminergic neurons in the ventral tegmental area of mice with intermittent methamphetamine treatment
Author(s) -
Kurokawa Kazuhiro,
Shibasaki Masahiro,
Kiyokage Emi,
Mizuno Koji,
Toida Kazunori,
Ohkuma Seitaro
Publication year - 2011
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20953
Subject(s) - ventral tegmental area , ifenprodil , conditioned place preference , nmda receptor , ryanodine receptor , dopaminergic , methamphetamine , chemistry , meth , dopamine , pharmacology , receptor , neuroscience , biology , biochemistry , monomer , organic chemistry , acrylate , polymer
Excitatory synapses on dopaminergic neurons of the ventral tegmental area (VTA) represent an important role in psychostimulant‐induced rewarding effect. This study investigated the regulation of ryanodine receptor (RyR) and N ‐methyl‐ D ‐aspartate (NMDA) receptor expression in mice under intermittent methamphetamine (METH) treatment using a place preference procedure. RyR‐1 and ‐2 significantly increased in the VTA of mice with METH‐induced place preference, whereas RyR‐3 showed no changes. In addition, the levels of NR1, NR2A, and NR2B subunits were increased in the VTA. The METH‐induced place preference was inhibited by intracerebroventricular pretreatment with MK‐801, a noncompetitive NMDA receptor antagonist, and ifenprodil, a selective NR2B subunit‐containing NMDA receptor antagonist, in a dose‐dependent manner. Under these conditions, the increase of RyR‐1 and ‐2 in the VTA was significantly blocked by ifenprodil. The immunohistochemical analysis revealed the colocalization of RyR‐1 and ‐2 with NR2B subunits in dopaminergic neurons in the mouse VTA. These findings suggest that RyRs could be involved in the development of METH‐induced place preference and that NR2B subunit‐containing NMDA receptors in mice showing METH‐induced place preference play an important role in expression of RyRs. Synapse, 2011. © 2011 Wiley‐Liss, Inc.