title: Ifenprodil attenuates the acquisition and expression of methamphetamine-induced behavioral sensitization and activation of Ras-ERK1/2 cascade in the caudate putamen.
abstract: Chronic discontinuous use of many psychomotor stimulants leads to behavioral sensitization and, owing to it shares common mechanisms with relapse, most researchers use its animal model to explore the neurobiological mechanisms of addiction. Recent studies have proved that N-methyl-d-aspartate receptors (NMDARs) are implicated in psychomotor stimulant-induced behavioral sensitization. However, the function of GluN2B-containing NMDARs and their potential downstream cascade(s) in the acquisition and expression of behavioral sensitization to methamphetamine (METH) have not been explored. In this study, 2.5, 5, and 10mg/kg ifenprodil, the specific inhibitor of GluN2B, was used to explore the function of these receptors in distinct phases of behavioral sensitization to METH in mice. Then, using western blot, Ras, pERK1/2/ERK1/2, and ΔFosB levels in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were detected. Behavioral results showed that low-dose ifenprodil attenuated the acquisition and expression of behavioral sensitization to METH significantly. Western blot analysis revealed that pre-injection of low-dose ifenprodil in the acquisition markedly attenuated METH-induced ascent of Ras, pERK1/2/ERK1/2, and ΔFosB protein levels in the CPu. However, pre-treatment in the expression only affected the alterations of Ras and pERK1/2/ERK1/2 levels in the CPu. Moreover, chronic METH administration increased pERK1/2/ERK1/2 level in the NAc. In conclusion, GluN2B-containing NMDARs contribute to both the acquisition and expression of behavioral sensitization to METH in mice. Furthermore, the acquisition phase might be mediated by the Ras-ERK1/2-ΔFosB cascade in the CPu while the expression phase may be regulated by the Ras-ERK1/2 cascade in the CPu.
authors.affiliation: School of Forensic Science and Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: xjtutopll@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: qcc0706@163.com.
authors.forename: Chuchu
authors.initials: C
authors.lastname: Qiao
authors.affiliation: School of Forensic Science and Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: ronicechen@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: School of Forensic Science and Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: 1414568425@qq.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Qian
authors.affiliation: School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710033, PR China. Electronic address: litao-hy@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hou
authors.affiliation: School of Forensic Science and Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science and Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: litao050428@xjtu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: School of Forensic Science and Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science and Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: lxins@xjtu.edu.cn.
authors.forename: Xinshe
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011699:Putamen / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D008694:Methamphetamine; C010739:ifenprodil
keywords: N-methyl-d-aspartate receptor; behavioral sensitization; caudate putamen; ifenprodil; methamphetamine; nucleus accumbens