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Self-administration of the synthetic cathinones 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (α-PVP) in rhesus monkeys

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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.

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Abbreviations

MDPV:

3,4-Methylenedioxypyrovalerone

α-PVP:

α-Pyrrolidinopentiophenone

DAT:

Dopamine transporter

NET:

Norepinephrine transporter

SERT:

Serotonin transporter

PR:

Progressive ratio

TO:

Timeout

ANOVA:

Analysis of variance

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Acknowledgments

The authors would like to thank Jade Juarez, Krissian Martinez, Emily Spoliarch, and Samuel Womak for their excellent technical assistance in completing these studies.

Funding

This research was supported by a National Institutes of Health research grant from the National Institute on Drug Abuse (R01DA039146 [GTC]); the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute of Alcohol Abuse and Alcoholism provided support for the work conducted by the Molecular Targets and Medications Discovery Branch (KCR, AS), and by the Welch Foundation (Grant AQ-0039 [CPF]). Funding sources had no involvement beyond financial support of this study.

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Authors and Affiliations

  1. Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX, 78229, USA

    Gregory T. Collins & Charles P. France

  2. Addiction Research, Treatment & Training Center of Excellence, University of Texas Health Science Center, San Antonio, TX, 78229, USA

    Gregory T. Collins & Charles P. France

  3. South Texas Veterans Health Care System, San Antonio, TX, 78229, USA

    Gregory T. Collins

  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

    Agnieszka Sulima & Kenner C. Rice

  5. Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, 78229, USA

    Charles P. France

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  1. Gregory T. Collins
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Correspondence to Gregory T. Collins.

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Collins, G.T., Sulima, A., Rice, K.C. et al. Self-administration of the synthetic cathinones 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (α-PVP) in rhesus monkeys. Psychopharmacology 236, 3677–3685 (2019). https://doi.org/10.1007/s00213-019-05339-4

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  • DOI: https://doi.org/10.1007/s00213-019-05339-4

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