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Self-administration and behavioral economics of second-generation synthetic cathinones in male rats

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Abstract

Rationale

Synthetic cathinones have become increasingly available as drugs of abuse. Distribution of these drugs is made possible by altering the chemical structures of prohibited cathinones and marketing them under misleading labels. Very little is known about the relative reinforcing effectiveness of new synthetic cathinones relative to known drugs of abuse.

Objective

We examined self-administration of three second-generation synthetic cathinones: alpha-pyrrolidinopentiophenone (alpha-PVP), 4-methyl-N-ethylcathinone (4-MEC), and 4-methyl-alpha-pyrrolidinopropiophenone (4-MePPP) relative to methamphetamine.

Method

Male, Sprague-Dawley rats, implanted with intravenous catheters, were trained to self-administer methamphetamine (0.05 mg/kg/injection) under a fixed-ratio schedule. Following training, various doses of methamphetamine (0.006-0.1 mg/kg/injection), alpha-PVP (0.0015-0.1 mg/kg/injection), 4-MEC (0.1-3.2 mg/kg/injection), or 4-MePPP (0.1-0.8 mg/kg/injection) were available for self-administration in separate groups, followed by a behavioral-economics evaluation of the reinforcing effectiveness of each drug.

Results

For all drugs, at least one dose functioned as a reinforcer. Alpha-PVP and 4-MePPP maintained the highest numbers of infusions per session and both were more effective reinforcers relative to methamphetamine. 4-MEC and methamphetamine were not significantly different in terms of infusions per session or reinforcing effectiveness.

Conclusion

Emerging synthetic cathinones whose primary pharmacological mechanism is to block dopamine uptake but with little effects on monoamine release or serotonin uptake may have a greater degree of abuse potential compared with known abused stimulants.

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Authors and Affiliations

  1. Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA

    S.L. Huskinson, J.K. Rowlett & K.B. Freeman

  2. Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    J.E. Naylor, E.A. Townsend, J.K. Rowlett & K.B. Freeman

  3. Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA, 70433, USA

    J.K. Rowlett

  4. Center for Drug Discovery, Research Triangle Institute, Research Triangle Park, NC, 27709, USA

    B.E. Blough

Authors
  1. S.L. Huskinson
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  2. J.E. Naylor
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  3. E.A. Townsend
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  4. J.K. Rowlett
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  5. B.E. Blough
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  6. K.B. Freeman
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Corresponding author

Correspondence to S.L. Huskinson.

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Conflict of interest

The authors have no conflicts of interest to disclose. This research was supported by the University of Mississippi Medical Center’s Drug Abuse Development Fund and the National Institute on Drug Abuse (NIDA) grant R01 DA12970 to B.E.B. Preparation of this manuscript was supported by the above mentioned funding sources in addition to NIDA grants F32 DA037619 to S.L.H., R01 DA033795 and R01 DA011792 to J.K.R., and R01 DA027666 and R01 DA039167 to K.B.F.

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Huskinson, S., Naylor, J., Townsend, E. et al. Self-administration and behavioral economics of second-generation synthetic cathinones in male rats. Psychopharmacology 234, 589–598 (2017). https://doi.org/10.1007/s00213-016-4492-6

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  • DOI: https://doi.org/10.1007/s00213-016-4492-6

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