title: Effects of ifenprodil on morphine-induced conditioned place preference and spatial learning and memory in rats.
abstract: Drug addiction, as well as learning and memory, share common mechanisms in terms of neural circuits and intracellular signaling pathways. In the present study, the role of N-methyl-D-aspartate (NMDA) receptors, particularly those containing NR2B subunits, in morphine-induced conditioned place preference (CPP) and Morris water maze (MWM) learning and memory task was investigated. CPP was used as a paradigm for assessing the rewarding effect of morphine, and MWM was used to measure spatial learning and memory in male Sprague-Dawley rats. We found that ifenprodil, an antagonist highly selective for NR2B-containing NMDA receptors, dose-dependently blocked the development, maintenance and reinstatement of morphine-induced CPP, without evident impairment of the acquisition and retrieval of spatial memory in the MWM task. However, the consolidation of spatial memory was disrupted by a high dose (10 mg/kg) of ifenprodil. These results clearly demonstrate that NR2B-containing NMDA receptors are actively involved in addiction memory induced by morphine conditioning, but not in the acquisition and retrieval of spatial learning and memory. In conclusion, NR2B-containing NMDA receptors can be considered potential targets for the treatment of opiate addiction.
authors.affiliation: Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, 100083, Beijing, People's Republic of China.
authors.forename: Yao-Ying
authors.initials: YY
authors.lastname: Ma
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: Chang-Yong
authors.initials: CY
authors.lastname: Guo
authors.forename: Cai-Lian
authors.initials: CL
authors.lastname: Cui
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D009294:Narcotics; D010880:Piperidines; D009020:Morphine; C010739:ifenprodil