title: Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: Evidence of its abuse potential.
abstract: Methoxetamine (MXE) is an N-methyl-d-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to ketamine. Recently, there have been many reports regarding its use/misuse in humans which have resulted in serious or even fatal outcomes. Despite these reports, MXE is not controlled or regulated in many countries which may be partly due to the lack of scientific evidence regarding its abuse potential. Thus, in the present study we evaluated the abuse potential (rewarding and reinforcing effects) of MXE through the conditioned place preference (CPP) and self-administration (SA) tests in Sprague-Dawley rats. In addition, locomotor activity during the conditioning phase of the CPP was also analyzed. Ketamine was used as a reference drug. MXE (2.5 and 5mg/kg) induced significant CPP in rats, an effect comparable to that of ketamine (5mg/kg). Interestingly, MXE did not produce any locomotor alterations while ketamine decreased the locomotor activity of rats. In the SA test, rats showed modest self-administration of MXE (0.25, 0.5, 1.0mg/kg/infusion), while ketamine (0.5mg/kg/infusion) was robustly self-administered. These results demonstrate that MXE, similar to ketamine, has rewarding and reinforcing effects in rats. The present study strongly suggests that MXE has a potential for human abuse. In addition, the discrepant effects of MXE and ketamine on locomotor activity and rate of self-administration propose that the psychopharmacological effects of these drugs may diverge in some aspects. More importantly, this study advocates the careful monitoring and prompt regulation of MXE and its related substances.
authors: Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, South Korea.
authors: Chrislean Jun
authors: CJ
authors: Botanas
authors: Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, South Korea.
authors: June Bryan
authors: JB
authors: de la Peña
authors: Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, South Korea.
authors: Irene Joy
authors: IJ
authors: Dela Peña
authors: Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, South Korea.
authors: Reinholdgher
authors: R
authors: Tampus
authors: Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, South Korea.
authors: Robin
authors: R
authors: Yoon
authors: Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, South Korea.
authors: Hee Jin
authors: HJ
authors: Kim
authors: Laboratory of Medicinal Chemistry, School of Pharmacy, Kyunghee University, Seoul 130-701, South Korea.
authors: Yong Sup
authors: YS
authors: Lee
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
authors: Choon Gon
authors: CG
authors: Jang
authors: Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, South Korea. Electronic address: cheongjh@syu.ac.kr.
authors: Jae Hoon
authors: JH
authors: Cheong
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D003512:Cyclohexanones / Q000494:pharmacology*; D003514:Cyclohexylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D012646:Self Administration; D019966:Substance-Related Disorders / Q000523:psychology*
chemical_list: D003512:Cyclohexanones; D003514:Cyclohexylamines; D007649:Ketamine; C569113:2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone
keywords: Addiction; Conditioned place preference; Designer drugs; Ketamine; Methoxetamine; Self-administration