Gregory T Collins1,2,3, Agnieszka Sulima4, Kenner C Rice4, Charles P France5,6,7. 1. Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX, 78229, USA. CollinsG@uthscsa.edu. 2. Addiction Research, Treatment & Training Center of Excellence, University of Texas Health Science Center, San Antonio, TX, 78229, USA. CollinsG@uthscsa.edu. 3. South Texas Veterans Health Care System, San Antonio, TX, 78229, USA. CollinsG@uthscsa.edu. 4. Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20850, USA. 5. Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX, 78229, USA. 6. Addiction Research, Treatment & Training Center of Excellence, University of Texas Health Science Center, San Antonio, TX, 78229, USA. 7. Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, 78229, USA.
Abstract
RATIONALE: The availability and abuse of synthetic analogues of cathinone have increased dramatically around the world. Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone [MDPV] and α-pyrrolidinopentiophenone [α-PVP], are cocaine-like inhibitors of monoamine transporters and common constituents of "bath salts" or "flakka" preparations. Studies in rats suggest that MDPV and α-PVP are 3 to 4-fold more effective reinforcers than cocaine; however, comparisons of the relative reinforcing effectiveness of MDPV and α-PVP have not been reported in other species. OBJECTIVES: Accordingly, in the present study, 4 adult male rhesus monkeys responding under a progressive ratio schedule of reinforcement were used to characterize the reinforcing effects of MDPV and α-PVP and to compare directly these effects with those of cocaine and methamphetamine. RESULTS: MDPV was the most potent reinforcer, followed by α-PVP, methamphetamine, and cocaine. α-PVP was the most effective reinforcer, followed by MDPV, cocaine, and methamphetamine. In addition to making more responses to obtain MDPV and α-PVP, monkeys also responded for longer periods of time when MDPV or α-PVP was available compared with when either cocaine or methamphetamine was available for infusion. CONCLUSIONS: These studies confirm recent reports from rodents and provide strong evidence that the synthetic cathinones MDPV and α-PVP are capable of maintaining high levels of responding for prolonged periods of time, and that they function as more effective reinforcers than either cocaine or methamphetamine. The relative strength of these reinforcing effects may account for the high rates of "bath salts" use reported in humans.
RATIONALE: The availability and abuse of synthetic analogues of cathinone have increased dramatically around the world. Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone [MDPV] and α-pyrrolidinopentiophenone [α-PVP], are cocaine-like inhibitors of monoamine transporters and common constituents of "bath salts" or "flakka" preparations. Studies in rats suggest that MDPV and α-PVP are 3 to 4-fold more effective reinforcers than cocaine; however, comparisons of the relative reinforcing effectiveness of MDPV and α-PVP have not been reported in other species. OBJECTIVES: Accordingly, in the present study, 4 adult male rhesus monkeys responding under a progressive ratio schedule of reinforcement were used to characterize the reinforcing effects of MDPV and α-PVP and to compare directly these effects with those of cocaine and methamphetamine. RESULTS:MDPV was the most potent reinforcer, followed by α-PVP, methamphetamine, and cocaine. α-PVP was the most effective reinforcer, followed by MDPV, cocaine, and methamphetamine. In addition to making more responses to obtain MDPV and α-PVP, monkeys also responded for longer periods of time when MDPV or α-PVP was available compared with when either cocaine or methamphetamine was available for infusion. CONCLUSIONS: These studies confirm recent reports from rodents and provide strong evidence that the synthetic cathinonesMDPV and α-PVP are capable of maintaining high levels of responding for prolonged periods of time, and that they function as more effective reinforcers than either cocaine or methamphetamine. The relative strength of these reinforcing effects may account for the high rates of "bath salts" use reported in humans.
Authors: Amy J Eshleman; Katherine M Wolfrum; John F Reed; Sunyoung O Kim; Tracy Swanson; Robert A Johnson; Aaron Janowsky Journal: J Pharmacol Exp Ther Date: 2016-10-31 Impact factor: 4.030
Authors: Adam R Winstock; Luke R Mitcheson; Paolo Deluca; Zoe Davey; Ornella Corazza; Fabrizio Schifano Journal: Addiction Date: 2010-08-23 Impact factor: 6.526
Authors: A Schneir; B T Ly; K Casagrande; M Darracq; S R Offerman; S Thornton; C Smollin; R Vohra; C Rangun; C Tomaszewski; R R Gerona Journal: Clin Toxicol (Phila) Date: 2014-08 Impact factor: 4.467
Authors: Katharine H Nelson; Hayley N Manke; Jacob M Bailey; Anna Vlachos; Karina J Maradiaga; Shihui Huang; Tania D Weiss; Kenner C Rice; Anthony L Riley Journal: Pharmacol Biochem Behav Date: 2021-10-08 Impact factor: 3.533
Authors: Iwona Ruchala; Umberto M Battisti; Vy T Nguyen; Rita Yu-Tzu Chen; Richard A Glennon; Jose M Eltit Journal: Toxicol Appl Pharmacol Date: 2021-03-27 Impact factor: 4.219
Authors: Fernando B de Moura; Alexander Sherwood; Thomas E Prisinzano; Carol A Paronis; Jack Bergman; Stephen J Kohut Journal: Pharmacol Biochem Behav Date: 2021-01-12 Impact factor: 3.533