RGD Reference Report - Evidence that MDMA ('ecstasy') increases cannabinoid CB2 receptor expression in microglial cells: role in the neuroinflammatory response in rat brain. - Rat Genome Database

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Evidence that MDMA ('ecstasy') increases cannabinoid CB2 receptor expression in microglial cells: role in the neuroinflammatory response in rat brain.

Authors: Torres, E  Gutierrez-Lopez, MD  Borcel, E  Peraile, I  Mayado, A  O'Shea, E  Colado, MI 
Citation: Torres E, etal., J Neurochem. 2010 Jan 12.
RGD ID: 2316187
Pubmed: (View Article at PubMed) PMID:20067581
DOI: Full-text: DOI: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-1beta (IL-1beta), the latter of which appears to be a consequence of the hyperthermic response and to be implicated in the neurotoxicity induced by the drug. Overexpression 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-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 IL-1beta 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.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Cnr1  (cannabinoid receptor 1)
Cnr2  (cannabinoid receptor 2)


Additional Information