NR2B-containing NMDA receptor is required for morphine-but not stress-induced reinstatement.
Glutamate receptors are known to be densely distributed in the forebrain rewarding circuits, and glutamatergic transmission is actively involved in the regulation of rewarding and reinstating effects of drugs of abuse. Here we investigated the possible involvement of the N-methyl-D-aspartate (NMDA) receptors in the reinstatement of extinguished morphine conditioned place preference (CPP) in rats. We found that previously extinguished morphine (3 mg/kg, i.p.) CPP was markedly reinstated by a priming injection of morphine (2 mg/kg, i.p.) or an acute environmental stressor (forced swim for 10 min), but not by the stress induced by a 24-h food deprivation. Parallel with this, protein levels of the NMDA receptor 2B subunit (NR2B) were elevated in the nucleus accumbens (NAc) and the hippocampus, but not the prefrontal cortex, of reinstated rats. Systemic administration of an NR2B selective antagonist ifenprodil (1, 3, 10 mg/kg, i.p.) attenuated the reinstatement induced by a priming morphine injection, although not by the forced swim. Ifenprodil (2.0 microg/rat) directly injected into the NAc shell or the CA1 region of the dorsal hippocampus produced a similar effect. These results indicate that the NR2B-containing NMDA receptors in the NAc and the dorsal hippocampus play a significant role in mediating the reinstatement of rewarding responses to morphine.
Ma
Yao-Ying
YY
Neuroscience Research Institute and Department of Neurobiology, Peking University Health Science Center, Key Laboratory of Neuroscience, the Ministry of Education and Ministry of Public Health, 38 Xueyuan Road, Beijing 100083, PR China.
Chu
Ning-Ning
NN
Guo
Chang-Yong
CY
Han
Ji-Sheng
JS
Cui
Cai-Lian
CL
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D005508:Food Deprivation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence / Q000523:psychology*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D012008:Recurrence; D012201:Reward; D013315:Stress, Psychological / Q000523:psychology*; D013550:Swimming / Q000523:psychology
D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D009294:Narcotics; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine; C010739:ifenprodil