Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

Journal of Neuroinflammation

Esther O'Shea¹  Maria I Colado¹  Maria D Gutierrez-Lopez¹  Elisa Torres¹  Andrea Mayado¹ 

[1] Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain

关键词: 5-HT;    neurotoxicity;    sIL-1RI;    IL-1ra;    IL-1β;    tolerance;    preconditioning;    MDMA;   

Others  :  1212986
DOI  :  10.1186/1742-2094-8-165

 received in 2011-09-20, accepted in 2011-11-24,  发布年份 2011

【 摘 要 】

Background

Preconditioning 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.

Methods

Male 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.

Results

Pretreatment 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.

Conclusions

These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

【 授权许可】

   
2011 Mayado et al; licensee BioMed Central Ltd.

【 图 表 】

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