3,4‐Methylenedioxymethamphetamine, mephedrone, and &bgr;‐phenylethylamine release dopamine from the cytoplasm by means of transporters and keep the concentration high and constant by blocking reuptake
G. Zsilla, Daniella E Hegyi, M. Baranyi, S. Vizi
European Journal of Pharmacology October 1, 2018 DOI: 10.1016/j.ejphar.2018.08.037 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Mouse brain tissue (nucleus accumbens, prefrontal cortex, and striatum slices and synaptosomes) |
| Interventions | MDMA mephedrone methylphenidate GBR 12909 nisoxetine |
| Measures | fractional release of [3H]-dopamine, high-pressure liquid chromatography, [3H]-dopamine uptake in synaptosomal P2 preparations |
| Topics | MDMA |
| Key findings | MDMA, mephedrone, and β-PEA increased resting, calcium-independent dopamine release from mouse nucleus accumbens and prefrontal cortex and inhibited dopamine uptake, while methylphenidate only potentiated stimulation-evoked release. The authors conclude these amphetamine-like drugs excessively raise non-vesicular, extrasynaptic dopamine and inhibit high-affinity transporters, which they argue likely contributes to their reinforcing and abusive potential. |
Abstract
ABSTRACT The addiction‐related behavioural effects of drugs of abuse are mediated by the mesocorticolimbic monoamine systems. We investigated the effects of 3,4‐methylenedioxymethamphetamine (MDMA), mephedrone, &bgr;‐phenylethylamine (&bgr;‐PEA) methylphenidate (MPH) on dopamine release from mouse perfused nucleus accumbens and prefrontal cortex slices. The fractional release of [3H]‐dopamine was measured at rest and in response to field stimulation. The distributions of [3H]‐dopamine and its metabolites were determined using high‐pressure liquid chromatography. The effect of drugs on [3H]‐dopamine uptake was measured in synaptosomal P2 preparations from the frontal cortex and striatum. Similar to MDMA, mephedrone &bgr;‐PEA increased the resting release of [3H]‐dopamine from the nucleus accumbens and prefrontal cortex in a [Ca2+]o‐independent manner, and the stimulation‐evoked release was also augmented. In contrast, MPH failed to affect the resting release but potentiated the release in response to axonal activity. Similar to dopamine transporter antagonist GBR 12909, mephedrone, MDMA and MPH biphasically inhibited the [3H]‐dopamine uptake. The administration of GBR 12909 and nisoxetine, or lowering the bath temperature prevented MDMA, mephedrone and &bgr;‐PEA from enhancing the resting, cytoplasmic release of [3H]‐dopamine, indicating the role of transporters in the release process. We conclude that amphetamine‐like drugs of abuse and the trace amine &bgr;‐PEA excessively increase the [Ca2+]o‐independent, non‐vesicular release of dopamine from the cytoplasm into the extrasynaptic space and inhibit the high‐affinity transporters, thereby maintaining a high ambient, non‐synaptic concentration of dopamine that may tonically control the activity of neurons equipped with dopamine receptors and is likely involved in the reinforcing effects and abusive potential of amphetamines.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 2
- Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy Journal of Psychopharmacology September 10, 2020
- A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA) Current Research in Toxicology May 27, 2022
Cites 4
- Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects Psychopharmacology May 27, 2017
- Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats British Journal of Pharmacology May 26, 2011
- Interactions between bupropion and 3,4-methylenedioxymethamphetamine in healthy subjects. Journal of Pharmacology and Experimental Therapeutics April 2015
- Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and clinical issues. Psychopharmacology April 2011