PMID- 15189347 OWN - NLM STAT- MEDLINE DCOM- 20040722 LR - 20221207 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 89 IP - 6 DP - 2004 Jun TI - 3,4-Methylenedioxymethamphetamine increases interleukin-1beta levels and activates microglia in rat brain: studies on the relationship with acute hyperthermia and 5-HT depletion. PG - 1445-53 AB - 3,4-Methylenedioxymethamphetamine (MDMA) administration to rats produces acute hyperthermia and 5-HT release. Interleukin-1beta (IL-1beta) is a pro-inflammatory pyrogen produced by activated microglia in the brain. We examined the effect of a neurotoxic dose of MDMA on IL-1beta concentration and glial activation and their relationship with acute hyperthermia and 5-HT depletion. MDMA, given to rats housed at 22 degrees C, increased IL-1beta levels in hypothalamus and cortex from 1 to 6 h and [(3)H]-(1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)3-isoquinolinecarboxamide) binding between 3 and 48 h. Increased immunoreactivity to OX-42 was also detected. Rats became hyperthermic immediately after MDMA and up to at least 12 h later. The IL-1 receptor antagonist did not modify MDMA-induced hyperthermia indicating that IL-1beta release is a consequence, not the cause, of the rise in body temperature. When MDMA was given to rats housed at 4 degrees C, hyperthermia was abolished and the IL-1beta increase significantly reduced. The MDMA-induced acute 5-HT depletion was prevented by fluoxetine coadministration but the IL-1beta increase and hyperthermia were unaffected. Therefore, the rise in IL-1beta is not related to the acute 5-HT release but is linked to the hyperthermia. Contrary to IL-1beta levels, microglial activation is not significantly modified when hyperthermia is prevented, suggesting that it might be a process not dependent on the hyperthermic response induced by MDMA. FAU - Orio, Laura AU - Orio L AD - Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain. FAU - O'Shea, Esther AU - O'Shea E FAU - Sanchez, Veronica AU - Sanchez V FAU - Pradillo, Jesus M AU - Pradillo JM FAU - Escobedo, Isabel AU - Escobedo I FAU - Camarero, Jorge AU - Camarero J FAU - Moro, Maria A AU - Moro MA FAU - Green, A Richard AU - Green AR FAU - Colado, M Isabel AU - Colado MI LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Interleukin 1 Receptor Antagonist Protein) RN - 0 (Interleukin-1) RN - 0 (Isoquinolines) RN - 0 (Serotonin Agents) RN - 0 (Serotonin Uptake Inhibitors) RN - 0 (Sialoglycoproteins) RN - 01K63SUP8D (Fluoxetine) RN - 333DO1RDJY (Serotonin) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - YNF83VN1RL (PK 11195) SB - IM MH - Acute Disease MH - Animals MH - Astrocytes/drug effects/metabolism MH - Binding, Competitive/drug effects/physiology MH - Body Temperature/drug effects MH - Brain/*drug effects/metabolism MH - Cerebral Cortex/drug effects/metabolism MH - Fever/*chemically induced/drug therapy/metabolism MH - Fluoxetine/pharmacology MH - Glial Fibrillary Acidic Protein/metabolism MH - Hypothalamus/drug effects/metabolism MH - Interleukin 1 Receptor Antagonist Protein MH - Interleukin-1/*metabolism MH - Isoquinolines/pharmacokinetics MH - Male MH - Microglia/*drug effects/metabolism MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Rats MH - Rats, Inbred Strains MH - Serotonin/deficiency/*metabolism MH - Serotonin Agents/pharmacology MH - Selective Serotonin Reuptake Inhibitors/pharmacology MH - Sialoglycoproteins/pharmacology MH - Temperature EDAT- 2004/06/11 05:00 MHDA- 2004/07/23 05:00 CRDT- 2004/06/11 05:00 PHST- 2004/06/11 05:00 [pubmed] PHST- 2004/07/23 05:00 [medline] PHST- 2004/06/11 05:00 [entrez] AID - JNC2443 [pii] AID - 10.1111/j.1471-4159.2004.02443.x [doi] PST - ppublish SO - J Neurochem. 2004 Jun;89(6):1445-53. doi: 10.1111/j.1471-4159.2004.02443.x.