title: A novel synthetic cathinone, 2-(methylamino)-1-(naphthalen-2-yl) propan-1-one (BMAPN), produced rewarding effects and altered striatal dopamine-related gene expression in mice.
abstract: The recreational use of synthetic cathinones has grown rapidly which prompted concerns from legal authorities and health care providers. However, in response to legislative regulations, synthesis of novel synthetic cathinones by introducing substituents in cathinone molecule has dramatically increased the diversity of these substances. Based on current trends, the aromatic ring is one of the popular sites in cathinone molecule being explored by designer-type modifications. In this study, we designed and synthesized a novel synthetic cathinone, 2-(methylamino)-1-(naphthalen-2-yl) propan-1-one (BMAPN), which has a naphthalene substituent on the aromatic ring. Thereafter, we determined whether BMAPN has rewarding and reinforcing effects through the conditioned place preference (CPP) test in mice and self-administration (SA) paradigm in rats. Locomotor sensitization was also assessed in mice during daily BMAPN treatment for 7days and drug challenge. Furthermore, we investigated the effects on BMAPN on dopamine-related genes in the striatum of mice using quantitative real-time polymerase chain reaction (qRT-PCR). BMAPN induced CPP at 10 and 30mg/kg and was modestly self-administered at 0.3mg/kg/infusion. Repeated BMAPN (30mg/kg) administration also produced locomotor sensitization. qRT-PCR analyses revealed decreased dopamine transporter and increased dopamine receptor D2 gene expression in the striatum of the BMAPN-treated mice. These data indicate that BMAPN has rewarding and reinforcing properties, which might be due to its effects on dopamine-related genes. The present study suggests that these findings may be useful in predicting abuse potential of future cathinone entities with aromatic ring substitutions.
authors.affiliation: Uimyung Research Institute for Neuroscience, School 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, School 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, School 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, School 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, School 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, School 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, School 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 / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism; D012201:Reward; D012646:Self Administration; D014316:Tritium; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: C000625170:2-(methylamino)-1-(naphthalen-2-yl) propan-1-one; D000470:Alkaloids; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D014316:Tritium; D008694:Methamphetamine; C023665:cathinone; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Abuse potential; Conditioned place preference; Locomotor sensitization; Self-administration; Synthetic cathinones