“Ecstasy” to addiction

Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA

Sean B. Dolan, Zhenglan Chen, Ren-Qi Huang, Michael B. Gatch

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in “Ecstasy” formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution. Self-administration of each compound was evaluated under a progressive ratio schedule of reinforcement. Each compound produced an inward current at the serotonin transporter, but little or no current at the dopamine transporter. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine, methylone and butylone substituted partially for DOM and fully for MDMA, whereas pentylone failed to substitute for DOM and substituted only partially for MDMA. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding produced by each test compound, but was least potent against pentylone. MDMA-appropriate responding was minimally affected by SCH23390. Each test compound was robustly self-administered with pentylone producing the greatest self-administration at the doses tested. Given the prevalence of synthetic cathinones in “Ecstasy” formulations, these data indicate that adulterated “Ecstasy” formulations may drive more compulsive drug use than those containing only MDMA.

Original languageEnglish
Pages (from-to)171-180
Number of pages10
JournalNeuropharmacology
Volume133
DOIs
StatePublished - 1 May 2018

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N-Methyl-3,4-methylenedioxyamphetamine
2,5-Dimethoxy-4-Methylamphetamine
Methamphetamine
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Self Administration
Reinforcement Schedule
Patch-Clamp Techniques
cathinone
pentylone
Pharmaceutical Preparations
SCH 23390

Keywords

  • Drug discrimination
  • MDMA
  • Patch clamp
  • Self-administration
  • Synthetic cathinones

Cite this

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abstract = "This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in “Ecstasy” formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution. Self-administration of each compound was evaluated under a progressive ratio schedule of reinforcement. Each compound produced an inward current at the serotonin transporter, but little or no current at the dopamine transporter. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine, methylone and butylone substituted partially for DOM and fully for MDMA, whereas pentylone failed to substitute for DOM and substituted only partially for MDMA. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding produced by each test compound, but was least potent against pentylone. MDMA-appropriate responding was minimally affected by SCH23390. Each test compound was robustly self-administered with pentylone producing the greatest self-administration at the doses tested. Given the prevalence of synthetic cathinones in “Ecstasy” formulations, these data indicate that adulterated “Ecstasy” formulations may drive more compulsive drug use than those containing only MDMA.",
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“Ecstasy” to addiction : Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA. / Dolan, Sean B.; Chen, Zhenglan; Huang, Ren-Qi; Gatch, Michael B.

In: Neuropharmacology, Vol. 133, 01.05.2018, p. 171-180.

Research output: Contribution to journalArticleResearchpeer-review

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