PMID- 23083295 OWN - NLM STAT- MEDLINE DCOM- 20130207 LR - 20171116 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 124 IP - 1 DP - 2013 Jan TI - Microglial and astroglial activation by 3,4-methylenedioxymethamphetamine (MDMA) in mice depends on S(+) enantiomer and is associated with an increase in body temperature and motility. PG - 69-78 LID - 10.1111/jnc.12060 [doi] AB - Evidence is accumulating to suggest that 3,4-methylenedioxymethamphetamine (MDMA) has neurotoxic and neuroinflammatory properties. MDMA is composed of two enantiomers with different biological activities. In this study, we evaluated the in vivo effects of S(+)-MDMA, R(-)-MDMA, and S(+)-MDMA in combination with R(-)-MDMA on microglial and astroglial activation compared with racemic MDMA, by assessment of complement type 3 receptor (CD11b) and glial fibrillary acidic protein (GFAP) immunoreactivity in the mouse striatum, nucleus accumbens, motor cortex, and substantia nigra. Motor activity and body temperature were also measured, to elucidate the physiological modifications paired with the observed glial changes. Similar to racemic MDMA (4 x 20 mg/kg), S(+)-MDMA (4 x 10 mg/kg) increased both CD11b and GFAP in the striatum, although to a lower degree, whereas R(-)-MDMA (4 x 10 mg/kg) did not induce any significant glial activation. Combined administration of S(+) plus R(-)-MDMA did not induce any further activation compared with S(+)-MDMA. In all other areas, only racemic MDMA was able to slightly activate the microglia, but not the astroglia, whereas enantiomers had no effect, either alone or in combination. Racemic MDMA and S(+)-MDMA similarly increased motor activity and raised body temperature, whereas R(-)-MDMA affected neither body temperature nor motor activity. Interestingly, the increase in body temperature was correlated with glial activation. The results show that no synergism, but only additivity of effects, is caused by the combined administration of S(+)- and R(-)-MDMA, and underline the importance of investigating the biochemical and behavioral properties of the two MDMA enantiomers to understand their relative contribution to the neuroinflammatory and neurotoxic effects of MDMA. CI - (c) 2012 International Society for Neurochemistry. FAU - Frau, Lucia AU - Frau L AD - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy. FAU - Simola, Nicola AU - Simola N FAU - Plumitallo, Antonio AU - Plumitallo A FAU - Morelli, Micaela AU - Morelli M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121115 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (CD11b Antigen) RN - 0 (Hallucinogens) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Astrocytes/*drug effects MH - Body Temperature/*drug effects MH - Brain/cytology/drug effects MH - CD11b Antigen/metabolism MH - Drug Interactions MH - Hallucinogens/chemistry/*toxicity MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microglia/*drug effects MH - Motor Activity/*drug effects MH - N-Methyl-3,4-methylenedioxyamphetamine/chemistry/*toxicity MH - Stereoisomerism EDAT- 2012/10/23 06:00 MHDA- 2013/02/08 06:00 CRDT- 2012/10/23 06:00 PHST- 2012/07/26 00:00 [received] PHST- 2012/10/04 00:00 [revised] PHST- 2012/10/09 00:00 [accepted] PHST- 2012/10/23 06:00 [entrez] PHST- 2012/10/23 06:00 [pubmed] PHST- 2013/02/08 06:00 [medline] AID - 10.1111/jnc.12060 [doi] PST - ppublish SO - J Neurochem. 2013 Jan;124(1):69-78. doi: 10.1111/jnc.12060. Epub 2012 Nov 15.