PMID- 15337264 OWN - NLM STAT- MEDLINE DCOM- 20041217 LR - 20151119 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 367 IP - 3 DP - 2004 Sep 9 TI - Microglial activation is a pharmacologically specific marker for the neurotoxic amphetamines. PG - 349-54 AB - Neurotoxic amphetamines cause damage to monoamine nerve terminals of the striatum by unknown mechanisms. Microglial activation contributes to the neuronal damage that accompanies injury, disease, and inflammation, but a role for these cells in amphetamine-induced neurotoxicity has received little attention. We show presently that D-methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), D-amphetamine, and p-chloroamphetamine, each of which has been linked to dopamine (DA) or serotonin nerve terminal damage, result in microglial activation in the striatum. The non-neurotoxic amphetamines l-methamphetamine, fenfluramine, and DOI do not have this effect. All drugs that cause microglial activation also increase expression of glial fibrillary acidic protein (GFAP). At a minimum, microglial activation serves as a pharmacologically specific marker for striatal nerve terminal damage resulting only from those amphetamines that exert neurotoxicity. Because microglia are known to produce many of the reactive species (e.g., nitric oxide, superoxide, cytokines) that mediate the neurotoxicity of the amphetamine-class of drugs, their activation could represent an early and essential event in the neurotoxic cascade associated with high-dose amphetamine intoxication. FAU - Thomas, David M AU - Thomas DM AD - Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2125 Scott Hall, 540 E Canfield, Detroit, MI 48201, USA. FAU - Dowgiert, Jennifer AU - Dowgiert J FAU - Geddes, Timothy J AU - Geddes TJ FAU - Francescutti-Verbeem, Dina AU - Francescutti-Verbeem D FAU - Liu, Xiuli AU - Liu X FAU - Kuhn, Donald M AU - Kuhn DM LA - eng GR - DA014392/DA/NIDA NIH HHS/United States GR - DA10756/DA/NIDA NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Dopamine Agents) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Lectins) RN - 44RAL3456C (Methamphetamine) RN - 64-12-0 (p-Chloroamphetamine) RN - CK833KGX7E (Amphetamine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Amphetamine/*toxicity MH - Analysis of Variance MH - Animals MH - Blotting, Western/methods MH - Cell Count/methods MH - Corpus Striatum/cytology/*drug effects/metabolism MH - Dopamine Agents/*toxicity MH - Female MH - Glial Fibrillary Acidic Protein/metabolism MH - Immunohistochemistry/methods MH - Lectins MH - Methamphetamine/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Microglia/*drug effects/physiology MH - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology MH - p-Chloroamphetamine/pharmacology EDAT- 2004/09/01 05:00 MHDA- 2004/12/18 09:00 CRDT- 2004/09/01 05:00 PHST- 2004/05/11 00:00 [received] PHST- 2004/06/08 00:00 [revised] PHST- 2004/06/10 00:00 [accepted] PHST- 2004/09/01 05:00 [pubmed] PHST- 2004/12/18 09:00 [medline] PHST- 2004/09/01 05:00 [entrez] AID - S0304-3940(04)00767-0 [pii] AID - 10.1016/j.neulet.2004.06.065 [doi] PST - ppublish SO - Neurosci Lett. 2004 Sep 9;367(3):349-54. doi: 10.1016/j.neulet.2004.06.065.