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Behavioral Profiles and Underlying Transmitters/Circuits of Cathinone-Derived Psychostimulant Drugs of Abuse

  • Steven J. Simmons
  • Erin Kim
  • Taylor A. Gentile
  • Ali Murad
  • John W. Muschamp
  • Scott M. Rawls
Chapter
Part of the Current Topics in Neurotoxicity book series (Current Topics Neurotoxicity, volume 12)

Abstract

Plant-derived cathinone (found in khat of C. edulis, a shrub native to Horn of Africa and Arabian Peninsula) is structurally similar to amphetamine and produces psychosomatic, behaviorally activating effects. Alterations to one or more motifs of cathinone’s molecular structure can yield novel psychoactive compounds with greater potency, toxicity, and abuse liability than the parent compound. These synthetic cathinone drugs, including 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV), are manufactured in clandestine laboratories with intent for recreational use and have been the subject of intensive research on basic and preclinical levels over the past decade. For years, synthetic cathinone drugs avoided legal persecution by vending formulations in packages marked “not for human consumption.” Even after scheduling by the Drug Enforcement Agency, novel formulations of synthetic cathinone drugs continue to be seized across the United States and internationally with emergency room visits and postmortem toxicology reports supporting this drug class as a persisting public health concern. This chapter will provide evaluation of studies that examine the behavioral effects following synthetic cathinone use as well as provide discussion of the transmitters and circuits that underlie these effects. Similarly to cocaine, amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA), synthetic cathinone drugs work by elevating extracellular levels of monoamines by augmenting release or by blocking presynaptic uptake. In animal models, synthetic cathinone drugs produce place preference, acutely prime brain reward thresholds and are readily self-administered. Available evidence supports that the potently rewarding and reinforcing effects of certain synthetic cathinone drugs are likely mediated by preferential action at dopaminergic and noradrenergic transporters, while empathogenic effects more strongly align with augmentation of serotonin transmission. As additional compounds are designed throughout the United States and elsewhere, understanding the sites of action and behavioral effects remains the goals of our laboratory and others in ultimate effort to intervene and suppress addiction propensity of harmful cathinone-derived psychostimulant drugs.

Keywords

Addiction models Intracranial self-stimulation Place conditioning Reinforcement Reward Self-administration Synthetic cathinone(s) 

Abbreviations

2PMPA

2-(phosphonomethyl)-pentanedioic acid

4-FMC (flephedrone)

4-fluoromethcathinone

4-MEC

4-methylethylcathinone

4-MePPP

4-methyl-α-pyrrolidinopropiophenone

4-MMC (mephedrone)

4-methylmethcathinone

5-HT

Serotonin

BMAPN

2-(methylamino)-1-(naphthalene-2-yl) propan-1-one

DA

Dopamine

DAT

Dopamine transporter

FR

Fixed ratio

GCPII

Glutamate carboxypeptidase II

GLT1

Glutamate transporter 1

Hcrt/Ox

Hypocretin/orexin

ICSS

Intracranial self-stimulation

MACHP

2-cyclohexyl-2-(methylamino)-1-phenylethanone

MAOP

2-(methylamino)-1-phenyloctan-1-one

MDEC (ethylone)

3,4-methylenedioxyethylcathinone

MDMA

3,4-methylenedioxymethamphetamine

MDMC (methylone)

3,4-methylenedioxymethcathinone

MDPV

3,4-methylenedioxypyrovalerone

mexedrone

3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one

mGluR2/3

Metabotropic glutamate receptors 2 and 3

NA

Noradrenaline

NAAG

N-acetylaspartylglutamate

NAcc

Nucleus accumbens

naphyrone

Naphthylpyrovalerone

NET

Noradrenaline transporter

PIPP

α-piperidinopropiophenone

PIVT

α-piperidinopentiothiophenone

PR

Progressive ratio

SERT

Serotonin transporter

USV

Ultrasonic vocalization

VTA

Ventral tegmental area

α-PVP

α-pyrrolidinopentiophenone

Notes

Contributions and Acknowledgements

SJS wrote and edited this chapter with input from EK, TAG, AM, and JWM under direction of SMR. The authors appreciate grant support from the National Institute on Drug Abuse (R01 DA039139 and R21 DA032718 to SMR; P30 DA013429 to Ellen M. Unterwald).

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Steven J. Simmons
    • 1
  • Erin Kim
    • 1
  • Taylor A. Gentile
    • 1
  • Ali Murad
    • 1
  • John W. Muschamp
    • 1
  • Scott M. Rawls
    • 1
  1. 1.Lewis Katz School of MedicineTemple UniversityPhiladelphiaUSA

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