title: The abuse potential of two novel synthetic cathinones with modification on the alpha-carbon position, 2-cyclohexyl-2-(methylamino)-1-phenylethanone (MACHP) and 2-(methylamino)-1-phenyloctan-1-one (MAOP), and their effects on dopaminergic activity.
abstract: The recreational use of synthetic cathinones has dramatically increased in recent years, which is partly due to easy accessibility and ability of synthetic cathinones to exert rewarding effects similar to cocaine and methamphetamine. Many synthetic cathinones have already been scheduled in several countries; however, novel and diverse synthetic cathinones are emerging at an unprecedented rate, often outpacing regulatory processes. Recently, designer modifications of the basic cathinone molecule are usually performed on the alpha-carbon position. In this study, we designed and synthesized two novel synthetic cathinones with substituents on alpha-carbon position, [1] 2-cyclohexyl-2-(methylamino)-1-phenylethanone (MACHP), and [2] 2-(methylamino)-1-phenyloctan-1-one (MAOP). Then, we evaluated their rewarding and reinforcing effects through the conditioned place preference (CPP) in mice and self-administration (SA) test in rats. Locomotor activity was also assessed in mice during daily MACHP or MAOP treatment for 7days and drug challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. MACHP and MAOP produced CPP at 10 and 30mg/kg. In the SA test, MACHP (1mg/kg/infusion), but not MAOP, was self-administered. Both MACHP and MAOP induced locomotor sensitization in mice. qRT-PCR analyses showed that MACHP and MAOP reduced dopamine transporter gene expression in the striatum. These data indicate that MACHP and MAOP may have rewarding properties, which might be attributed to their ability to affect the dopaminergic activity. These findings may be useful in predicting the abuse potential and hasten the regulation of future cathinone entities with similar modifications.
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul 01795, Republic of Korea.
authors.forename: Chrislean Jun
authors.initials: CJ
authors.lastname: Botanas
authors.affiliation: Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
authors.forename: Seong Shoon
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul 01795, Republic of Korea.
authors.forename: June Bryan
authors.initials: JB
authors.lastname: de la Peña
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul 01795, Republic of Korea.
authors.forename: Irene Joy
authors.initials: IJ
authors.lastname: Dela Peña
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul 01795, Republic of Korea.
authors.forename: Mikyung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul 01795, Republic of Korea.
authors.forename: Taeseon
authors.initials: T
authors.lastname: Woo
authors.affiliation: Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
authors.forename: Joung-Wook
authors.initials: JW
authors.lastname: Seo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Park
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul 01795, Republic of Korea. Electronic address: msheejin@gmail.com.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul 01795, Republic of Korea. Electronic address: cheongjh@syu.ac.kr.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D059290:Dopaminergic Neurons / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012646:Self Administration; D019966:Substance-Related Disorders
chemical_list: D000470:Alkaloids; D050483:Dopamine Plasma Membrane Transport Proteins; C023665:cathinone
keywords: Abuse potential; Conditioned place preference; Locomotor sensitization; Self-administration; Synthetic cathinones