title: Levo-tetrahydropalmatine attenuates the development and expression of methamphetamine-induced locomotor sensitization and the accompanying activation of ERK in the nucleus accumbens and caudate putamen in mice.
abstract: Levo-tetrahydropalmatine (l-THP) is an alkaloid purified from corydalis and has been used in many traditional Chinese herbal preparations for its analgesic, sedative, and hypnotic properties. Previous studies indicated that l-THP has modest antagonist activity against dopamine receptors and thus it might have potential therapeutic effects on drug addiction. However, whether and how l-THP contributes to methamphetamine (METH)-induced locomotor sensitization remains unclear. Therefore, the current study aims to examine the roles of l-THP in the development and expression of METH-induced locomotor sensitization as well as the accompanying extracellular-regulated kinase (ERK) activation in the nucleus accumbens (NAc), caudate putamen (CPu) and prefrontal cortex (PFc) in mice. We found that moderate doses of METH (0.5 and 2 mg/kg) induced hyper-locomotor activity in mice on all METH injection days whereas high dose of METH (5 mg/kg)-treated mice displayed only acute locomotor response to METH and severe stereotyped behaviors on the first day after drug injection. Interestingly, only 2 mg/kg dose of METH-induced locomotor sensitization which was accompanied by the activation of ERK1/2 in the NAc and CPu in mice. Although l-THP (5 and 10 mg/kg) per se did not induce obvious changes in locomotor activities in mice, its co-administration with METH could significantly attenuate acute METH-induced hyper-locomotor activity, the development and expression of METH-induced locomotor sensitization, and the accompanying ERK1/2 activation in the NAc and CPu. These results suggest that l-THP has potential therapeutic effect on METH-induced locomotor sensitization, and the underlying molecular mechanism might be related to its inhibitory effect on ERK1/2 phosphorylation in the NAc and CPu.
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: N
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore 21201, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: chenteng@mail.xjtu.edu.cn.
authors.forename: T
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects* / Q000502:physiology; D001600:Berberine Alkaloids / Q000494:pharmacology*; D015153:Blotting, Western; D059333:Central Nervous System Sensitization / Q000187:drug effects / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D011699:Putamen / Q000187:drug effects / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D001600:Berberine Alkaloids; D000697:Central Nervous System Stimulants; C014215:tetrahydropalmatine; D008694:Methamphetamine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: CPu; ERK; MAPK; METH; NAc; PFc; THP; caudate putamen; extracellular-regulated kinase; levo-tetrahydropalmatine; locomotor sensitization; methamphetamine; mitogen-activated protein kinase; nucleus accumbens; prefrontal cortex; tetrahydropalmatine