Jae Hoon Cheong1, Mee Jung Choi2, Choon-Gon Jang3, Yong Sup Lee4, Sooyeun Lee5, Hee Jin Kim1, Joung-Wook Seo2, Seong Shoon Yoon6,7. 1. Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul, 01795, Republic of Korea. 2. Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea. 3. Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea. 4. Laboratory of Medicinal Chemistry, School of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea. 5. College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu, 42601, Republic of Korea. 6. Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea. ssyoon@kitox.re.kr. 7. Human and Environmental Toxicology, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea. ssyoon@kitox.re.kr.
Abstract
RATIONALE: Synthetic cathinones are chemical derivatives of cathinone that are pharmacologically similar to cocaine and methamphetamine. Recently, abuse of synthetic cathinones among young people has increased. OBJECTIVES: The present study aimed to characterize the behavioral effects of alpha-pyrrolidinopentiothiophenone (PVT), an analog of alpha-pyrrolidinovalerophenone and second-generation synthetic cathinone, as well as to evaluate its abuse potential, using conditioned place preference, intravenous self-administration (SA), and drug discrimination paradigms in rodent models. RESULTS: Alpha-PVT produced a significant place preference in mice at doses of 10, 30, and 50 mg/kg. In the SA experiment, alpha-PVT (0.1, 0.3, and 1.0 mg/kg/infusion) produced an inverted U-shaped dose-effect curve in rats. Under a progressive ratio schedule of reinforcement, there appeared to be a positive relationship between alpha-PVT dose and the breakpoints for alpha-PVT reinforcement. Additionally, alpha-PVT fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine in rats. CONCLUSIONS: Our results indicate that alpha-PVT has rewarding and reinforcing effects and shares the interoceptive effects of cocaine and methamphetamine. To the best of our knowledge, the present study is the first to show that alpha-PVT has reinforcing properties when delivered on its own, which suggests possible abuse liability in humans.
RATIONALE: Synthetic cathinones are chemical derivatives of cathinone that are pharmacologically similar to cocaine and methamphetamine. Recently, abuse of synthetic cathinones among young people has increased. OBJECTIVES: The present study aimed to characterize the behavioral effects of alpha-pyrrolidinopentiothiophenone (PVT), an analog of alpha-pyrrolidinovalerophenone and second-generation synthetic cathinone, as well as to evaluate its abuse potential, using conditioned place preference, intravenous self-administration (SA), and drug discrimination paradigms in rodent models. RESULTS: Alpha-PVT produced a significant place preference in mice at doses of 10, 30, and 50 mg/kg. In the SA experiment, alpha-PVT (0.1, 0.3, and 1.0 mg/kg/infusion) produced an inverted U-shaped dose-effect curve in rats. Under a progressive ratio schedule of reinforcement, there appeared to be a positive relationship between alpha-PVT dose and the breakpoints for alpha-PVT reinforcement. Additionally, alpha-PVT fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine in rats. CONCLUSIONS: Our results indicate that alpha-PVT has rewarding and reinforcing effects and shares the interoceptive effects of cocaine and methamphetamine. To the best of our knowledge, the present study is the first to show that alpha-PVT has reinforcing properties when delivered on its own, which suggests possible abuse liability in humans.
Entities:
Keywords:
Abuse potential; Alpha-pyrrolidinopentiothiophenone; Conditioned place preference; Drug discrimination; Rodents; Self-administration; Synthetic cathinone derivatives
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