Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA
Andrea Mayado, Elisa Torres, Maria D Gutierrez-Lopez, Maria I Colado, Esther O'Shea
Journal of Neuroinflammation December 1, 2011 DOI: 10.1186/1742-2094-8-165 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male Dark Agouti rats |
| Interventions | MDMA (3 mg/kg i.p.) sIL-1RI (3 μg i.c.v.) IL-1β (2.5 pg intracortical) |
| Dose | 3 mg/kg, 12.5 mg/kg, 3 μg, 2.5 pg |
| Duration | 96 hours between low dose and neurotoxic dose; assessments at 1 h, 3 h, 7 days, and between 3 h and 96 h |
| Topics | MDMA Serotonin |
| Citations | 8 |
| Key findings | Interleukin-1β mediates the delayed preconditioning effect of low-dose MDMA against subsequent neurotoxic MDMA-induced serotonin transporter loss. |
Abstract
AbstractBackgroundPreconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA.MethodsMale Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.). IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later.ResultsPretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v.) prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical) given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning.ConclusionsThese results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 13
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- 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
- Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration British Journal of Pharmacology February 1, 1999
- Effect of Repeated (‘Binge’) Dosing of MDMA to Rats Housed at Normal and High Temperature on Neurotoxicdamage to Cerebral 5-Ht and Dopamine Neurones Journal of Psychopharmacology September 1, 2004
- MDMA‐induced neurotoxicity: long‐term effects on 5‐HT biosynthesis and the influence of ambient temperature British Journal of Pharmacology June 12, 2006
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