PMID- 17181558 OWN - NLM STAT- MEDLINE DCOM- 20070320 LR - 20131121 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 100 IP - 3 DP - 2007 Feb TI - In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. PG - 617-27 AB - p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of 'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with marked changes in serotonergic neurotransmission, but the long-term effects of PMA are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on in vitro measures of neurodegeneration: serotonin (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2 weeks later indices of SERT function were measured. [(3)H]5-HT uptake into synaptosomes and [(3)H]cyanoimipramine binding to the SERT were significantly reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that in vitro measures of 5-HT axonal degeneration do not necessarily predict potential compensatory mechanisms that maintain SERT function under basal conditions. FAU - Callaghan, Paul D AU - Callaghan PD AD - Department of Physiology, The University of Texas Health Science Center at San Antonio, TX 78229-3900, USA. FAU - Owens, W Anthony AU - Owens WA FAU - Javors, Martin A AU - Javors MA FAU - Sanchez, Teresa A AU - Sanchez TA FAU - Jones, David J AU - Jones DJ FAU - Irvine, Rodney J AU - Irvine RJ FAU - Daws, Lynette C AU - Daws LC LA - eng GR - R01 MH64489/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20061201 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Amphetamines) RN - 0 (Serotonin Agents) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 333DO1RDJY (Serotonin) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - OVB8F8P39Q (4-methoxyamphetamine) SB - IM MH - Amphetamines/*pharmacology MH - Animals MH - Binding, Competitive/drug effects/physiology MH - Hippocampus/*drug effects/metabolism/physiopathology MH - Male MH - Metabolic Clearance Rate/drug effects/physiology MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Presynaptic Terminals/drug effects/metabolism MH - Radioligand Assay MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/*metabolism/pharmacokinetics MH - Serotonin Agents/pharmacology MH - Serotonin Plasma Membrane Transport Proteins/drug effects/*metabolism MH - Synaptosomes/chemistry/metabolism MH - Wallerian Degeneration/chemically induced/metabolism/physiopathology EDAT- 2006/12/22 09:00 MHDA- 2007/03/21 09:00 CRDT- 2006/12/22 09:00 PHST- 2006/12/22 09:00 [pubmed] PHST- 2007/03/21 09:00 [medline] PHST- 2006/12/22 09:00 [entrez] AID - JNC4247 [pii] AID - 10.1111/j.1471-4159.2006.04247.x [doi] PST - ppublish SO - J Neurochem. 2007 Feb;100(3):617-27. doi: 10.1111/j.1471-4159.2006.04247.x. Epub 2006 Dec 1.