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Psychopharmacology

, Volume 233, Issue 10, pp 1981–1990 | Cite as

Reinforcing and neurochemical effects of the “bath salts” constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats

  • Charles W. Schindler
  • Eric B. Thorndike
  • Steven R. Goldberg
  • Kurt R. Lehner
  • Nicholas V. Cozzi
  • Simon D. Brandt
  • Michael H. Baumann
Original Investigation

Abstract

Rationale

3,4-Methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) are synthetic drugs found in so-called “bath salts” products. Both drugs exert their effects by interacting with monoamine transporter proteins. MDPV is a potent uptake blocker at transporters for dopamine and norepinephrine while methylone is a non-selective releaser at transporters for dopamine, norepinephrine, and serotonin (5-HT).

Objectives

We hypothesized that prominent 5-HT-releasing actions of methylone would render this drug less reinforcing than MDPV.

Methods

To test this hypothesis, we compared behavioral effects of MDPV and methylone using intravenous (i.v.) self-administration on a fixed-ratio 1 schedule in male rats. Additionally, neurochemical effects of the drugs were examined using in vivo microdialysis in nucleus accumbens, in a separate cohort of rats.

Results

MDPV self-administration (0.03 mg/kg/inj) was acquired rapidly and reached 40 infusions per session, similar to the effects of cocaine (0.5 mg/kg/inj), by the end of training. In contrast, methylone self-administration (0.3 and 0.5 mg/kg/inj) was acquired slowly, and response rates only reached 20 infusions per session by the end of training. In dose substitution studies, MDPV and cocaine displayed typical inverted U-shaped dose-effect functions, but methylone did not. In vivo microdialysis revealed that i.v. MDPV (0.1 and 0.3 mg/kg) increased extracellular dopamine while i.v. methylone (1 and 3 mg/kg) increased extracellular dopamine and 5-HT.

Conclusions

Our findings support the hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs. Nevertheless, MDPV and methylone are both self-administered by rats, suggesting these drugs possess significant abuse liability in humans.

Keywords

3,4-Methylenedioxypyrovalerone (MDPV) Methylone Cocaine Self-administration Microdialysis Rats 

Notes

Acknowledgments

This research was supported by the Intramural Research Program of NIH, NIDA. The authors have no conflicts of interest to report. We dedicate this paper to our colleague and friend Steven R. Goldberg who passed away suddenly on November 25, 2014.

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Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2015

Authors and Affiliations

  • Charles W. Schindler
    • 1
  • Eric B. Thorndike
    • 1
  • Steven R. Goldberg
    • 1
  • Kurt R. Lehner
    • 2
  • Nicholas V. Cozzi
    • 3
  • Simon D. Brandt
    • 4
  • Michael H. Baumann
    • 2
  1. 1.Preclinical Pharmacology Section, Intramural Research Program of the National Institute on Drug AbuseNational Institutes of HealthBaltimoreUSA
  2. 2.Designer Drug Research Unit, Intramural Research Program of the National Institute on Drug AbuseNational Institutes of HealthBaltimoreUSA
  3. 3.Department of Cell and Regenerative BiologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  4. 4.School of Pharmacy and Biomolecular SciencesLiverpool John Moores UniversityLiverpoolUK

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