Evidence that MDMA (‘ecstasy’) increases cannabinoid CB2 receptor expression in microglial cells: role in the neuroinflammatory response in rat brain
Elisa Torres, María Dolores Gutiérrez‐lópez, Érika Borcel, Inés Peraile, Andrea Mayado, Esther O’shea, María Isabel Colado
Journal of Neurochemistry January 12, 2010 DOI: 10.1111/j.1471-4159.2010.06578.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult Dark Agouti rats |
| Intervention | MDMA |
| Dose | 12.5 mg/kg MDMA; JWH-015 given 48 h, 24 h, and 0.5 h before MDMA and 1 h and/or 6 h later |
| Duration | 7 days for neurotoxicity assessment |
| Topics | MDMA Serotonin |
| Keywords | Neurotoxicity Microglia Neuroinflammation Pharmacology Agonist Cannabinoid receptor Proinflammatory cytokine Endocrinology |
| Citations | 44 |
| Key findings | CB2 receptor activation with JWH-015 reduces MDMA-induced neuroinflammation and provides partial neuroprotection against serotonin neurotoxicity in rats. |
Abstract
J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06578.x Abstract 3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) produces selective long‐lasting serotonergic neurotoxicity in rats. The drug also produces acute hyperthermia which modulates the severity of the neurotoxic response. In addition, MDMA produces signs of neuroinflammation reflected as microglial activation and an increase in the release of interleukin‐1β, the latter of which appears to be a consequence of the hyperthermic response and to be implicated in the neurotoxicity induced by the drug. Over‐expression of the cannabinoid CB2 receptor in microglia during non‐immune and immune pathological conditions is thought to be aimed at controlling the production of neurotoxic factors such as proinflammatory cytokines. Our objective was to study the pattern of CB2 receptor expression following MDMA and to examine the effect of JWH‐015 (a CB2 agonist) on the MDMA‐induced neuroinflammatory response as well as 5‐hydroxytryptamine (5‐HT) neurotoxicity. Adult Dark Agouti rats were given MDMA (12.5 mg/kg, i.p.) and killed 3 h or 24 h later for the determination of CB2 receptor expression. JWH‐015 was given 48 h, 24 h and 0.5 h before MDMA and 1 h and/or 6 h later and animals were killed for the determination of microglial activation (3 h and 24 h) and 5‐HT neurotoxicity (7 days). MDMA increased CB2 receptor expression shortly after administration and these receptors were found in microglia. JWH‐015 decreased MDMA‐induced microglial activation and interleukin‐1β release and slightly decreased MDMA‐induced 5‐HT neurotoxicity. In conclusion, CB2 receptor activation reduces the neuroinflammatory response following MDMA and provides partial neuroprotection against the drug.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 10
- Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine Life Science July 24, 2013
- Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA): regulation by CB2 receptors and implications for neurotoxicity Journal of Neuroinflammation August 6, 2011
- Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA Journal of Neuroinflammation December 1, 2011
- Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications Pharmaceuticals June 17, 2011
- MDMA (3,4-methylenedioxy-methamphetamine) Drug Addiction Mechanisms in the Brain April 8, 2024
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Cites 10
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa Annals of the New York Academy of Sciences October 1, 1990
- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
- MDMA‐induced neurotoxicity: long‐term effects on 5‐HT biosynthesis and the influence of ambient temperature British Journal of Pharmacology June 12, 2006
and 5 more in the library