title: Levo-tetrahydropalmatine inhibits the acquisition of ketamine-induced conditioned place preference by regulating the expression of ERK and CREB phosphorylation in rats.
abstract: Levo-tetrahydropalmatine (l-THP) is an alkaloid purified from the Chinese herbs Corydalis and Stephania and has been used in many traditional Chinese herbal preparations for its sedative, analgesic and hypnotic properties. Previous studies demonstrated that l-THP has antagonistic activity on dopamine receptors; thus, it may have potential therapeutic effects on drug abuse. However, whether l-THP affects ketamine-induced conditioned place preference (CPP) remains unclear. Therefore, the present study was designed to evaluate the effects of l-THP on the rewarding behavior of ketamine through CPP. Results revealed that ketamine (5, 10 and 15mg/kg) induced CPP in rats. Furthermore, Ketamine (10mg/kg) promoted the phosphorylation of extracellular-regulated kinase (ERK) and cAMP responsive element binding protein (CREB) in the hippocampus (Hip) and caudate putamen (CPu), but not in the prefrontal cortex (PFc). l-THP (20mg/kg) co-administered with ketamine during conditioning inhibited the acquisition of ketamine-induced CPP in rats. Furthermore, l-THP (20mg/kg) prevented the enhanced phosphorylation of ERK and CREB in CPu and Hip. These results suggest that l-THP has potential therapeutic effects on ketamine-induced CPP. The underlying molecular mechanism may be related to its inhibitory effect on ERK and CREB phosphorylation in Hip and CPu. The present data supports the potential use of l-THP for the treatment of ketamine addiction.
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No 56, Xinjian Nan Road, Taiyuan, 030001, Shanxi, China; School of Forensic Medicine, Shanxi Medical University, No 56, Xinjian Nan Road, Taiyuan, 030001, Shanxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.affiliation: The Tumor Hospital of Shanxi Province, Taiyuan, Shanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Du
authors.affiliation: School of Forensic Medicine, Shanxi Medical University, No 56, Xinjian Nan Road, Taiyuan, 030001, Shanxi, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.affiliation: Biomedical and Life Science, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK; Second Hospital, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
authors.affiliation: School of Forensic Medicine, Shanxi Medical University, No 56, Xinjian Nan Road, Taiyuan, 030001, Shanxi, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Feng
authors.affiliation: School of Forensic Medicine, Shanxi Medical University, No 56, Xinjian Nan Road, Taiyuan, 030001, Shanxi, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Su
authors.affiliation: School of Forensic Medicine, Shanxi Medical University, No 56, Xinjian Nan Road, Taiyuan, 030001, Shanxi, China. Electronic address: cxddy_2004@sxmu.edu.cn.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Forensic Medicine, Shanxi Medical University, No 56, Xinjian Nan Road, Taiyuan, 030001, Shanxi, China.
authors.forename: Ke-Ming
authors.initials: KM
authors.lastname: Yun
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011699:Putamen / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014150:Antipsychotic Agents; D001600:Berberine Alkaloids; D018691:Excitatory Amino Acid Antagonists; C014215:tetrahydropalmatine; D007649:Ketamine; D050882:CREB-Binding Protein; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Conditioned place preference; Extracellular regulated protein kinase; Ketamine; Levo-tetrahydropalmatine; cAMP responsive element binding protein