title: The Effects of 4-Methylethcathinone on Conditioned Place Preference, Locomotor Sensitization, and Anxiety-Like Behavior: A Comparison with Methamphetamine.
abstract: BACKGROUND
  4-Methylethcathinone is a drug that belongs to the second generation of synthetic cathinones, and recently it has been ranked among the most popular "legal highs". Although it has similar in vitro neurochemical actions to other drugs such as cocaine, the behavioral effects of 4-methylethcathinone remain to be determined.
  
  
  METHODS
  The addictive potential and locomotor potentiation by 4-methylethcathinone were investigated in rats using the conditioned place preference and sensitization paradigm. Methamphetamine was used as a positive control. Because synthetic cathinones can have psychological effects, we also examined anxiety-like behavior using the elevated plus maze.
  
  
  RESULTS
  A conditioning dose of 10 mg/kg 4-methylethcathinone was able to induce conditioned place preference and reinstatement (following 2 weeks of withdrawal). Acute or repeated injections of 4-methylethcathinone at 3 or 10mg/kg failed to alter locomotor activity. At 30 mg/kg, however, acute 4-methylethcathinone increased locomotor activity compared with saline, while chronic 4-methylethcathinone induced a delayed and attenuated sensitization compared with methamphetamine. Additionally, repeated daily injections of 4-methylethcathinone (30 mg/kg) reduced, whereas methamphetamine increased time spent by rats in the open arm of an elevated plus maze compared with saline injections. Interestingly, a 2-week withdrawal period following chronic injections of 4-methylethcathinone or methamphetamine increased time spent in the open arm in all rats.
  
  
  CONCLUSIONS
  The rewarding properties of 4-methylethcathinone were found to be dissociated from its effects on locomotor activity. Additionally, chronic 4-methylethcathinone use may trigger abnormal anxious behaviors. These behavioral effects caused by 4-methylethcathinone appear to last even after a withdrawal period.
authors.affiliation: Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing, PR China (Ms Xu, Mr Bai, Ms Xu, Ms Liu); National Institute on Drug Dependence, Peking University, Beijing, PR China (Mr Qiu, Mr Zhang, and Dr Shen); Institute of Neurosciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China (Mr Zhang); The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC Australia (Dr Kim).
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing, PR China (Ms Xu, Mr Bai, Ms Xu, Ms Liu); National Institute on Drug Dependence, Peking University, Beijing, PR China (Mr Qiu, Mr Zhang, and Dr Shen); Institute of Neurosciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China (Mr Zhang); The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC Australia (Dr Kim).
authors.forename: Yi
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing, PR China (Ms Xu, Mr Bai, Ms Xu, Ms Liu); National Institute on Drug Dependence, Peking University, Beijing, PR China (Mr Qiu, Mr Zhang, and Dr Shen); Institute of Neurosciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China (Mr Zhang); The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC Australia (Dr Kim).
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing, PR China (Ms Xu, Mr Bai, Ms Xu, Ms Liu); National Institute on Drug Dependence, Peking University, Beijing, PR China (Mr Qiu, Mr Zhang, and Dr Shen); Institute of Neurosciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China (Mr Zhang); The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC Australia (Dr Kim).
authors.forename: Yanping
authors.initials: Y
authors.lastname: Βai
authors.affiliation: Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing, PR China (Ms Xu, Mr Bai, Ms Xu, Ms Liu); National Institute on Drug Dependence, Peking University, Beijing, PR China (Mr Qiu, Mr Zhang, and Dr Shen); Institute of Neurosciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China (Mr Zhang); The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC Australia (Dr Kim).
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing, PR China (Ms Xu, Mr Bai, Ms Xu, Ms Liu); National Institute on Drug Dependence, Peking University, Beijing, PR China (Mr Qiu, Mr Zhang, and Dr Shen); Institute of Neurosciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China (Mr Zhang); The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC Australia (Dr Kim).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing, PR China (Ms Xu, Mr Bai, Ms Xu, Ms Liu); National Institute on Drug Dependence, Peking University, Beijing, PR China (Mr Qiu, Mr Zhang, and Dr Shen); Institute of Neurosciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China (Mr Zhang); The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC Australia (Dr Kim).
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing, PR China (Ms Xu, Mr Bai, Ms Xu, Ms Liu); National Institute on Drug Dependence, Peking University, Beijing, PR China (Mr Qiu, Mr Zhang, and Dr Shen); Institute of Neurosciences, Guangzhou Medical University, Guangzhou, Guangdong, PR China (Mr Zhang); The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC Australia (Dr Kim). shenhw@hsc.pku.edu.cn.
authors.forename: Hao-wei
authors.initials: HW
authors.lastname: Shen
mesh_terms: D000662:Amphetamines / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D002491:Central Nervous System Agents / Q000494:pharmacology* / Q000633:toxicity; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology* / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects*; D011427:Propiophenones / Q000494:pharmacology* / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects; D013375:Substance Withdrawal Syndrome
chemical_list: D000662:Amphetamines; D002491:Central Nervous System Agents; D011427:Propiophenones; D008694:Methamphetamine; C585202:4-methylethcathinone
keywords: 4-methylethcathinone; CPP; elevated plus maze; locomotor sensitization