title: p38 mitogen-activated protein kinase activation in amygdala mediates κ opioid receptor agonist U50,488H-induced conditioned place aversion.
abstract: κ opioid receptor agonists produce aversive effects in rodents, however the underlying mechanisms remain unclear. Activation of p38 mitogen-activated protein kinase (MAPK) has been discovered to play a critical role in the modulation of affective behaviors. The present study was undertaken to detect the possible involvement of p38 MAPK in the aversive effects induced by κ opioid receptor activation. We found that the κ opioid receptor agonist trans-(±)-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide methanesulfonate salt (U50,488H) produced significant place aversion in mice as measured by the conditioned place preference procedure, accompanied with significant p38 MAPK activation in the amygdala, but not in the nucleus accumbens and hippocampus. Stereotaxic microinjection of the p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridy-l)-1H-imidazole (SB203580) into amygdala significantly inhibited p38 MAPK activation and completely blocked the conditioned place aversion in mice. Thus, these results suggested that activation of p38 MAPK in the amygdala was required to mediate κ opioid receptor-induced aversive behavior.
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Collaborative Innovation Center for Brain Science, Shanghai 201203, China.
authors.forename: G-Y
authors.initials: GY
authors.lastname: Zan
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Collaborative Innovation Center for Brain Science, Shanghai 201203, China.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: The Department of Neurosurgery, Changhai Hospital, Shanghai 200433, China.
authors.forename: J-C
authors.initials: JC
authors.lastname: Chen
authors.affiliation: The Department of Neurosurgery, Changhai Hospital, Shanghai 200433, China.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: The Department of Neurosurgery, Changhai Hospital, Shanghai 200433, China.
authors.forename: C-H
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Collaborative Innovation Center for Brain Science, Shanghai 201203, China.
authors.forename: J-R
authors.initials: JR
authors.lastname: Chai
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Collaborative Innovation Center for Brain Science, Shanghai 201203, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Department of Neurosurgery, Changhai Hospital, Shanghai 200433, China. Electronic address: huxiaowu25@sina.com.
authors.forename: X-W
authors.initials: XW
authors.lastname: Hu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: schuxh@126.com.
authors.forename: X-H
authors.initials: XH
authors.lastname: Shu
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Collaborative Innovation Center for Brain Science, Shanghai 201203, China. Electronic address: jgliu@mail.shcnc.ac.cn.
authors.forename: J-G
authors.initials: JG
authors.lastname: Liu
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000679:Amygdala / Q000201:enzymology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D018712:Analgesics, Non-Narcotic; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: 488H; U50; conditioned place aversion; p38 MAPK; κ opioid receptor