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Behavioral economic analysis of the reinforcing effects of “bath salts” mixtures: studies with MDPV, methylone, and caffeine in male Sprague-Dawley rats

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Abstract

Rationale

“Bath salts” preparations often contain combinations of synthetic cathinones (e.g., 3,4-methylenedioxymethcathinone [methylone], 3,4-methylenedioxypyrovalerone [MDPV]), and caffeine, and evidence suggests that mixtures of synthetic cathinones and caffeine (e.g., MDPV + caffeine or methylone + caffeine) can be more potent and/or effective reinforcers than predicted for an additive interaction.

Objective

To use demand curve analyses to compare the reinforcing effectiveness of MDPV and methylone to mixtures of MDPV + caffeine and methylone + caffeine.

Methods

Male Sprague-Dawley rats acquired methylone self-administration (0.32 mg/kg/inf) under a fixed ratio (FR) 1 schedule of reinforcement and generated full dose-response curves for methylone (0.01–1 mg/kg/inf) under an FR5 schedule of reinforcement. Demand curves were then obtained for methylone, MDPV, caffeine, and methylone + caffeine and MDPV + caffeine mixtures by increasing the FR across sessions according to the following series: 3, 10, 18, 32, 56, 100, 178, etc.

Results

Self-administration of methylone was rapidly acquired by 87.5% of rats and was maintained across a range of doses, producing an inverted U-shaped dose-response curve. Rank order demand for the individual constituents was MDPV > methylone > caffeine. Demand for the 3:1 (but not 10:1) methylone + caffeine mixture was greater than that for methylone alone, and demand for MDPV alone was similar to both MDPV + caffeine mixtures evaluated.

Conclusions

These studies provide additional evidence that although methylone is an effective reinforcer, combining methylone with caffeine results in an enhanced reinforcing effectiveness compared to methylone alone. Thus, abused “bath salts” preparations containing synthetic cathinones and caffeine may have higher abuse liability than preparations containing only synthetic cathinones.

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Abbreviations

NPSs:

New psychoactive substances

α-PVP:

alpha-Pyrrolidinopentiophenone

α-PPP:

α-Pyrrolidinopropiophenone

MDPV:

3,4-Methylenedioxypyrovalerone

MDPBP:

3,4-Methylenedioxy-α-pyrrolidinobutiophenone

MDPPP:

3,4-Methylenedioxy-α-pyrrolidinopropiophenone

4-MePPP:

4-Methyl-alpha-pyrrolidinopropiophenone

4-MEC:

4-Methyl-N-ethylcathinone

DAT:

Dopamine transporter

NET:

Norepinephrine transporter

SERT:

Serotonin transporter

PR:

Progressive ratio

FR:

Fixed ratio

TO:

Timeout

SEM:

Standard error of the mean

CIs:

Confidence intervals

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Funding

This study was supported by National Institutes of Health grants R01DA039146 (GTC) and T32DA031115 (BMG) and by the Intramural Research Programs of the National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism (KCR).

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Authors and Affiliations

  1. Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr – MC# 7764, San Antonio, TX, 78229, USA

    Brenda M. Gannon, Melson P. Mesmin & Gregory T. Collins

  2. Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, MD, USA

    Agnieszka Sulima & Kenner C. Rice

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

    Gregory T. Collins

Authors
  1. Brenda M. Gannon
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  2. Melson P. Mesmin
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  3. Agnieszka Sulima
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  4. Kenner C. Rice
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  5. Gregory T. Collins
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Corresponding author

Correspondence to Gregory T. Collins.

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The authors declare that they have no conflict of interest.

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This article belongs to a Special Issue on Bath Salts.

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Gannon, B.M., Mesmin, M.P., Sulima, A. et al. Behavioral economic analysis of the reinforcing effects of “bath salts” mixtures: studies with MDPV, methylone, and caffeine in male Sprague-Dawley rats. Psychopharmacology 236, 1031–1041 (2019). https://doi.org/10.1007/s00213-018-5046-x

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  • DOI: https://doi.org/10.1007/s00213-018-5046-x

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