Active vaccination reduces reinforcing effects of MDPV in male Sprague-Dawley rats trained to self-administer cocaine

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 cue-induced 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 drug-conjugate vaccines in substance abuse disorders will likely require concurrent behavior modification therapy.

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Funding

This research was supported by the National Institute on Drug Abuse DA039195, T32 GM106999, and F31DA046121 to SJM. The studies described in this support were submitted in partial fulfillment of Samantha J. McClenahan’s dissertation: McClenahan et al. (2019) Development and preclinical testing of a 3,4-methylenedioxypyrovalerona-like vaccine in rats. Doctoral dissertation, University of Arkansas for Medical Sciences, Little Rock, AR.

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The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Participation in research design: SJM, MGG, WEF, and SMO. Conducted experiments: SJM and MGG. Performed data analysis: SJM and WEF.

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Correspondence to William E. Fantegrossi.

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McClenahan, S.J., Gunnell, M.G., Owens, S.M. et al. Active vaccination reduces reinforcing effects of MDPV in male Sprague-Dawley rats trained to self-administer cocaine. Psychopharmacology (2020). https://doi.org/10.1007/s00213-020-05558-0

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Keywords

  • 3,4-Methylenedioxypyrovalerone
  • Drug-conjugate vaccine
  • Self-administration