“Ecstasy” to Addiction: Mechanisms and Reinforcing Effects of Three Synthetic Cathinone Analogs of MDMA
Sean B. Dolan, Zhenglan Chen, Renqi Huang, Michael B. Gatch
Neuropharmacology January 31, 2018 DOI: 10.1016/j.neuropharm.2018.01.020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Methylone Butylone Pentylone SCH23390 |
| Topics | Addiction MDMA |
| Key points | Pentylone produced the greatest self-administration among the tested compounds, indicating that adulterated Ecstasy formulations may drive more compulsive drug use than those containing only MDMA. |
Abstract
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. HighlightsMDMA, methylone, butylone, and pentylone are serotonin transporter substrates.Each drug produces methamphetamine‐like discriminative stimulus effects.Methylone and butylone produce largely serotonergic discriminative stimulus effects.Pentylone produces predominately dopaminergic discriminative stimulus effects.Pentylone is self‐administered to greater degree than butylone or MDMA.
Comparable studies
Other preclinical and animal studies on MDMA for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Rats | 2001 | Experimental study | |
| Neurotoxic Effects of MDMA on Brain Serotonin Neurons: Evidence from Neurochemical and Radioligand Binding Studiesa Rats and rhesus monkeys | 1990 | Review | |
| Enhancement of conditioned place preference response to cocaine in rats following subchronic administration of 3,4-methylenedioxymethamphetamine (MDMA) Male Sprague-Dawley rats | 2000 | Experimental study | |
| Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration Rats | 2012 | Observational cohort | |
| Profile of MDMA Self-Administration from a Large Cohort of Rats: MDMA Develops a Profile of Dependence with Extended Testing Rats | 2012 | Observational cohort | n = 128 |
Citations in the library
Cited by 15
- A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy Frontiers in Psychiatry October 12, 2022
- Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation ACS Chemical Neuroscience March 9, 2021
- MDMA-assisted psychotherapy for the treatment of PTSD: A systematic review and meta-analysis of randomized controlled trials (RCTs). Neuropsychopharmacology Reports December 1, 2024
- Self-Administration of Entactogen Psychostimulants Dysregulates Gamma-Aminobutyric Acid (GABA) and Kappa Opioid Receptor Signaling in the Central Nucleus of the Amygdala of Female Wistar Rats Frontiers in Behavioral Neuroscience December 16, 2021
- Bioisosteric analogs of MDMA: Improving the pharmacological profile? Journal of Neurochemistry September 1, 2024
and 10 more in the library
Cites 13
- Who is ‘Molly’? MDMA adulterants by product name and the impact of harm-reduction services at raves Journal of Psychopharmacology July 10, 2017
- An Exploration of the History and Controversies Surrounding MDMA and MDA Journal of Psychoactive Drugs September 1, 2001
- The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in “Bath Salts” Journal of Addiction Research & Therapy December 1, 2012
- A three-choice discrimination procedure dissociates the discriminative stimulus effects of d-amphetamine and (±)-MDMA in rats. Experimental and Clinical Psychopharmacology 2000
- Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine. Behavioural Pharmacology June 1, 2017
and 8 more in the library