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Repeated administration of synthetic cathinone 3,4-methylenedioxypyrovalerone persistently increases impulsive choice in rats

Hyatt, William S.a; Berquist, Michael D.a; Chitre, Neha M.b; Russell, Lauren N.a; Rice, Kenner C.c; Murnane, Kevin S.b; Fantegrossi, William E.a

doi: 10.1097/FBP.0000000000000492
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3,4-Methylenedioxypyrovalerone (MDPV) is a selective catecholamine reuptake inhibitor abused for its psychostimulant properties. This study examined if MDPV administration alters impulsive choice measured by delay discounting in rats. Three groups of rats were tested in daily delay discounting sessions to determine the effects of acute cocaine (1.0–30.0 mg/kg), MDPV (0.1–3.0 mg/kg), or saline on mean adjusted delay (MAD). Dose-dependent decreases in MAD were elicited only by acute MDPV, which also suppressed operant responding at the highest dose. Next, rats received post-session injections (30.0 mg/kg cocaine, 3.0 mg/kg MDPV, or saline) every other day for a total of 10 injections. MAD increased during saline treatment, did not change during cocaine treatment, and was reduced during MDPV treatment. In dose-effect re-determinations, no acute drug effects on MAD were observed, but compared to the initial dose-effect determination, MDPV suppressed operant responding in more animals, with zero animals completing trials at the highest dose. All saline and MDPV-treated subjects were sacrificed, and striatal and cortical dopamine levels were quantified by HPLC. These studies indicate that administration of MDPV may increase impulsive choice acutely and persistently. These proimpulsive effects are possibly mediated by increases in striatal dopamine turnover.

aDepartment of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas

bDepartment of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, Georgia

cDrug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA

Received 17 September 2018 Accepted as revised 14 April 2019

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Correspondence to William E. Fantegrossi, PhD, Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72207, USA, E-mail: WEFantegrossi@uams.edu

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