Active vaccination reduces reinforcing effects of MDPV in male Sprague-Dawley rats trained to self-administer cocaine
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ORIGINAL INVESTIGATION
Active vaccination reduces reinforcing effects of MDPV in male Sprague-Dawley rats trained to self-administer cocaine Samantha J. McClenahan 1 & Melinda G. Gunnell 1 & S. Michael Owens 1 & William E. Fantegrossi 1 Received: 8 December 2019 / Accepted: 18 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone abused for its cocaine-like psychostimulant effects in “bath salts” products. While there are currently no pharmacotherapies for MDPV abuse, rodent studies suggest immunotherapy may offer a feasible treatment option. Objectives These studies tested the capacity of active vaccination to reduce the reinforcing effects of MDPV in Sprague-Dawley rats. Methods Rats acquired cocaine self-administration (0.32 mg/kg/inf) on an FR1 schedule. Dose-effect functions for cocaine (0.032–1.0 mg/kg/inf) and MDPV (0.001–0.32 mg/kg/inf) were determined under an FR5 schedule. Rats in the vaccine group were immunized during cocaine self-administration. All rats transitioned to a progressive-ratio (PR) schedule to establish breakpoints for cocaine (0.1–1.0 mg/kg/inf) and MDPV (0.01–0.32 mg/kg/inf). Responding was extinguished, and cueinduced and MDPV-primed reinstatement (0.56 mg/kg, IP) were evaluated. Results No endpoints of cocaine self-administration differed between groups, but the ED50 for MDPV self-administration was significantly lower in control relative to vaccinated rats. Under the PR schedule, MDPV was ~ 2.5-fold more potent in maintaining responding in control than vaccinated rats, but Emax was not different between groups. Vaccination did not reduce MDPV-primed reinstatement, perhaps due to a decrease in antibody titer. Conclusions Vaccination did not alter acquisition of cocaine self-administration, demonstrating pharmacological selectivity and suggesting that the vaccine did not affect learning or motivation, while effectively reducing the potency of MDPV as a reinforcer. The protective effects of the vaccine were surmounted by large unit doses of MDPV, suggesting maximal efficacy of drugconjugate vaccines in substance abuse disorders will likely require concurrent behavior modification therapy. Keywords 3,4-Methylenedioxypyrovalerone . Drug-conjugate vaccine . Self-administration
Introduction 3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive synthetic cathinone that produces adverse health effects in humans, including impaired driving, psychosis, agitation, and death by adverse cardiac events (Sivagnanam et al. 2013; Wyman et al. 2013). MDPV is one of the most commonly found synthetic cathinones in mixtures sold under deceptive names such as “plant food” or “bath salts” (Spiller
* William E. Fantegrossi [email protected] 1
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham, Slot 638, Little Rock, AR 72205, USA
et al. 2011). MDPV use in the USA spiked in 2011 and decreased after it became scheduled under th
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