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Stereoselective effects of the second-generation synthetic cathinone α-pyrrolidinopentiophenone (α-PVP): assessments of conditioned taste avoidance in rats

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Abstract

Rationale

Work with α-pyrrolidinopentiophenone (α-PVP), a second-generation synthetic cathinone, has been generally limited to the racemate. Given that with other synthetic cathinones, there are behavioral and neurochemical differences between their enantiomers, differences may also be seen with α-PVP.

Objectives

The present study assessed the relative contribution of each enantiomer to the aversive effects of racemic-α-PVP by comparing their ability to induce a conditioned taste avoidance.

Methods

Adult male Sprague-Dawley rats were exposed every other day for four exposures to a novel saccharin solution followed immediately by an injection of 0 (saline vehicle) or 1.5, 3, or 6 mg/kg of S-, R-, or racemic-α-PVP (IP). On alternating days, all subjects were given access to water to assess any unconditioned effects of α-PVP on general fluid consumption.

Results

Rats injected with the racemate and S-isomer of α-PVP displayed avoidance of the drug-associated saccharin solution, although this avoidance was dose-dependent only for the subjects injected with the racemate. There was no evidence of taste avoidance in animals injected with the R-enantiomer at any dose tested. Animals injected with 3 mg/kg racemic-α-PVP did not differ in avoidance from those treated with 1.5 mg/kg of the S-enantiomer, but subjects treated with 6 mg/kg racemic-α-PVP displayed a significantly stronger avoidance than those treated with 3 mg/kg S-α-PVP.

Conclusions

The present work suggests that the aversive effects of racemic α-PVP are mediated primarily by its S-isomer. The fact that at the highest dose tested (6 mg/kg), the racemate induces an avoidance greater than the simple additive effects of the S- and R-isomers (at 3 mg/kg) suggests that while the R-isomer may not induce taste avoidance at this dose, it may interact synergistically with the S-isomer in mediating the effects of the racemic mixture. These results were discussed in terms of similar effects with other behavioral and physiological endpoints reported with a number of psychostimulants and suggest that the enantiomers of α-PVP are an important variable in characterizing its behavioral effects.

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Funding

This research was supported in part by a grant from the Mellon Foundation to A.L.R. The Mellon Foundation had no further role in the study design, data collection, analysis and interpretation, the writing of the report or the decision to submit the manuscript for publication. The work of the Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch (MTMDB), National Institute on Drug Abuse (NIDA), and National Institute of Alcohol Abuse and Alcoholism (NIAAA) was supported by the NIH Intramural Research Programs of the National Institute on Drug Abuse (NIDA) and the National Institute of Alcohol Abuse and Alcoholism (NIAAA).

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Authors and Affiliations

  1. Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, DC, 20016, USA

    Katharine H. Nelson, Raul López-Arnau, Briana J. Hempel, Peter To, Hayley N. Manke, Madeline E. Crissman, Matthew M. Clasen & Anthony L. Riley

  2. Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain

    Raul López-Arnau

  3. Drug Design and Synthesis Section, National Institute on Drug Abuse (NIDA), National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, MD, 20892, USA

    Kenner C. Rice

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  1. Katharine H. Nelson
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  2. Raul López-Arnau
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  4. Peter To
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Corresponding author

Correspondence to Katharine H. Nelson.

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All procedures adhered to the Guidelines for the Care and Use of Laboratory Animals (National Research Council, 2011) and the Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (National Research Council, 2003) and were approved by the Institutional Animal Care and Use Committee at American University.

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This article belongs to a Special Issue on Bath Salts

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Nelson, K.H., López-Arnau, R., Hempel, B.J. et al. Stereoselective effects of the second-generation synthetic cathinone α-pyrrolidinopentiophenone (α-PVP): assessments of conditioned taste avoidance in rats. Psychopharmacology 236, 1067–1077 (2019). https://doi.org/10.1007/s00213-018-5070-x

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