title: The new designer drug buphedrone produces rewarding properties via dopamine D1 receptor activation.
abstract: Substituted cathinones are synthetic analogs of the active components of natural products and are widely abused worldwide. However, the rewarding properties of these agents have not yet been evaluated. In this study, we investigated the abuse potential of buphedrone [2-(methylamino)-1-phenylbutan-1-one, α-methylamino-butyrophenone] and its effects on the mesolimbic dopaminergic system in mice using conditioned place preference (CPP) analysis, a self-administration test, a locomotor activity test, a behavioral sensitization test and Western blot analysis. Treatment with buphedrone supported CPP and self-administration, enhanced locomotor activity and produced behavioral sensitization when mice were challenged with methamphetamine. SCH23390, a D1 dopamine antagonist, prevented buphedrone-induced CPP, whereas raclopride, a D2 dopamine antagonist, had no effect. SCH23390 also blocked locomotor activity increase by buphedrone, while raclopride partially attenuated locomotor activation. Western blot analysis revealed that repeated buphedrone treatment increased D1 dopamine receptor expression in the dorsal striatum and nucleus accumbens in mice. Collectively, these findings suggest the abuse potential of buphedrone and demonstrate the involvement of the dopaminergic system in the establishment of its rewarding properties.
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors: Ji-Hwan
authors: JH
authors: Oh
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors: Ji-Young
authors: JY
authors: Hwang
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors: Sa-Ik
authors: SI
authors: Hong
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors: Shi-Xun
authors: SX
authors: Ma
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors: Jee-Yeon
authors: JY
authors: Seo
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors: Seok-Yong
authors: SY
authors: Lee
authors: Neurotoxicology Program, College of Pharmacy, Korea Institute of Drug Abuse, Kangwon National University, Korea.
authors: Hyoung-Chun
authors: HC
authors: Kim
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors: Choon-Gon
authors: CG
authors: Jang
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002090:Butyrophenones / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015198:Designer Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors; D016674:Hylobatidae; D008124:Locomotion / Q000187:drug effects*; D008694:Methamphetamine; D008744:Methylamines / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D012201:Reward; D012646:Self Administration
chemical_list: D001552:Benzazepines; D002090:Butyrophenones; D015198:Designer Drugs; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; C583261:Drd1 protein, mouse; D008744:Methylamines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D020891:Raclopride; D008694:Methamphetamine; C572409:buphedrone
keywords: Behavioral sensitization; SCH23390; buphedrone; conditioned place preference; dopaminergic transmission; locomotor activity; raclopride; self-administration