PMID- 10029234 OWN - NLM STAT- MEDLINE DCOM- 19990504 LR - 20131121 IS - 0887-4476 (Print) IS - 0887-4476 (Linking) VI - 31 IP - 3 DP - 1999 Mar 1 TI - N-tert-butyl-alpha-phenylnitrone protects against 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats. PG - 169-77 AB - The present study examined the effect of N-tert-butyl-alpha-phenylnitrone (PBN) on 3,4-methylenedioxmathamphetamine (MDMA)-induced depletion of serotonin in the CNS. Rats were treated with two concurrent injections of MDMA (20 mg/kg, s.c.), PBN (50-400 mg/kg dissolved in ethanol, 50 mg/ml of 25% ethanol, i.p.), saline or 25% ethanol, alone or in combination, 6 h apart, and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injection for 5 h. Monoamine levels in the tissue were measured by HPLC. Density of the 5-HT transporters was assayed by [3H]paroxetine binding. Rectal temperature of rats increased after MDMA, decreased after PBN, ethanol, PBN plus ethanol, and MDMA plus ethanol, and was not significantly altered after MDMA plus PBN. Levels of 5-HT and 5-HIAA in the frontal cortex, hippocampus, striatum, and brain stem of rats decreased significantly after MDMA or MDMA plus ethanol, but not after MDMA plus PBN, PBN plus ethanol (PBN dissolved in ethanol), or ethanol as compared to the saline controls. Levels of 5-HT and 5-HIAA in the brain tissues of rats treated with MDMA plus PBN were elevated as compared to those treated with MDMA plus saline. Similar results were observed in the density of 5-HT transporters in the frontal cortex and hippocampus. These results indicate that scavenging of free radicals of MDMA metabolites or reactive oxygen species by PBN and with lowering of body temperature protected against MDMA-induced depletion of serotonin transmitter. FAU - Yeh, S Y AU - Yeh SY AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. LA - eng PT - Journal Article PL - United States TA - Synapse JT - Synapse (New York, N.Y.) JID - 8806914 RN - 0 (Cyclic N-Oxides) RN - 0 (Free Radicals) RN - 0 (Nitrogen Oxides) RN - 0 (Serotonin Agents) RN - 0 (Spin Labels) RN - 333DO1RDJY (Serotonin) RN - 3I91332OPG (phenyl-N-tert-butylnitrone) RN - 54-16-0 (Hydroxyindoleacetic Acid) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Body Temperature Regulation/drug effects MH - Brain/cytology/*drug effects/metabolism MH - Brain Stem/drug effects/metabolism MH - Cyclic N-Oxides MH - Free Radicals MH - Frontal Lobe/drug effects/metabolism MH - Hippocampus/drug effects/metabolism MH - Hydroxyindoleacetic Acid/metabolism MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*antagonists & inhibitors MH - Neurons/drug effects/metabolism MH - Nitrogen Oxides/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/*deficiency MH - Serotonin Agents/*pharmacology MH - Spin Labels EDAT- 1999/02/24 03:02 MHDA- 2000/06/20 09:00 CRDT- 1999/02/24 03:02 PHST- 1999/02/24 03:02 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1999/02/24 03:02 [entrez] AID - 10.1002/(SICI)1098-2396(19990301)31:3<169::AID-SYN1>3.0.CO;2-N [pii] AID - 10.1002/(SICI)1098-2396(19990301)31:3<169::AID-SYN1>3.0.CO;2-N [doi] PST - ppublish SO - Synapse. 1999 Mar 1;31(3):169-77. doi: 10.1002/(SICI)1098-2396(19990301)31:3<169::AID-SYN1>3.0.CO;2-N.