title: Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA.
abstract: 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.
authors: Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors: Andrea
authors: A
authors: Mayado
authors: Elisa
authors: E
authors: Torres
authors: Maria D
authors: MD
authors: Gutierrez-Lopez
authors: Maria I
authors: MI
authors: Colado
authors: Esther
authors: E
authors: O'Shea
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004361:Drug Tolerance / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine