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
Summary
AI-generated from the abstractA low dose of MDMA given to rats 96 hours before a neurotoxic dose reduces damage to serotonin transporters and lowers elevated interleukin-1β levels while increasing interleukin-1 receptor antagonist levels. The low dose itself raises IL-1β at 3 hours and IL-1ra at 96 hours, and increases soluble IL-1 receptor type I expression. Blocking IL-1 signaling with sIL-1RI prevents this protective effect, while injecting IL-1β alone mimics the preconditioning, indicating that IL-1β is key in developing tolerance to MDMA neurotoxicity.
Study at a glance
| 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 |
| Citations | 8 |
| Key finding | 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.