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https://hdl.handle.net/2440/37290
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Type: | Journal article |
Title: | 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 |
Author: | Callaghan, P. Owens, W. Javors, M. Sanchez, T. Jones, D. Irvine, R. Daws, L. |
Citation: | Journal of Neurochemistry, 2007; 100(3):617-627 |
Publisher: | Blackwell Publishing Ltd |
Issue Date: | 2007 |
ISSN: | 0022-3042 1471-4159 |
Statement of Responsibility: | Paul D. Callaghan, W. Anthony Owens, Martin A. Javors, Teresa A. Sanchez, David J. Jones, Rodney J. Irvine and Lynette C. Daws |
Abstract: | 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. [3H]5-HT uptake into synaptosomes and [3H]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. |
Keywords: | chronoamperometry 3, 4-methylenedioxymethamphetamine neurodegeneration para-methoxyamphetamine serotonin serotonin transporter |
DOI: | 10.1111/j.1471-4159.2006.04247.x |
Published version: | http://www.blackwell-synergy.com/doi/abs/10.1111/j.1471-4159.2006.04247.x |
Appears in Collections: | Aurora harvest Pharmacology publications |
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