| 3,4-Methylenedioxymethamphetamine increases interleukin-1beta levels and activates microglia in rat brain: studies on the relationship with acute hyperthermia and 5-HT depletion. | |
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MedLine Citation:
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PMID: 15189347 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Laura Orio; Esther O'Shea; Veronica Sanchez; Jesus M Pradillo; Isabel Escobedo; Jorge Camarero; Maria A Moro; A Richard Green; M Isabel Colado |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neurochemistry Volume: 89 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 2004 Jun |
Date Detail:
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Created Date: 2004-06-10 Completed Date: 2004-07-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 1445-53 Citation Subset: IM |
Affiliation:
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Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Disease Animals Astrocytes / drug effects, metabolism Binding, Competitive / drug effects, physiology Body Temperature / drug effects Brain / drug effects*, metabolism Cerebral Cortex / drug effects, metabolism Fever / chemically induced*, drug therapy, metabolism Fluoxetine / pharmacology Glial Fibrillary Acidic Protein / metabolism Hypothalamus / drug effects, metabolism Interleukin 1 Receptor Antagonist Protein Interleukin-1 / metabolism* Isoquinolines / pharmacokinetics Male Microglia / drug effects*, metabolism N-Methyl-3,4-methylenedioxyamphetamine / pharmacology* Rats Rats, Inbred Strains Serotonin / deficiency, metabolism* Serotonin Agents / pharmacology Serotonin Uptake Inhibitors / pharmacology Sialoglycoproteins / pharmacology Temperature |
| Chemical | |
Reg. No./Substance:
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0/Glial Fibrillary Acidic Protein; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1; 0/Isoquinolines; 0/Serotonin Agents; 0/Serotonin Uptake Inhibitors; 0/Sialoglycoproteins; 42542-10-9/N-Methyl-3,4-methylenedioxyamphetamine; 50-67-9/Serotonin; 54910-89-3/Fluoxetine; 85340-56-3/PK 11195 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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