Repeated administration of the substituted amphetamine p-methoxyamphetamine produces reductions in cortical 5-HT transporter binding but not 5-HT content, unlike 3,4-methylenedioxyamethamphetamine

Callaghan, Paul D., Farrand, Kirsten, Salem, Abdallah, Hughes, Patrick, Daws, Lynette C. and Irvine, Rodney J. (2006) Repeated administration of the substituted amphetamine p-methoxyamphetamine produces reductions in cortical 5-HT transporter binding but not 5-HT content, unlike 3,4-methylenedioxyamethamphetamine. European journal of pharmacology, 546 1-3: 74-81. doi:10.1016/j.ejphar.2006.07.011


Author Callaghan, Paul D.
Farrand, Kirsten
Salem, Abdallah
Hughes, Patrick
Daws, Lynette C.
Irvine, Rodney J.
Title Repeated administration of the substituted amphetamine p-methoxyamphetamine produces reductions in cortical 5-HT transporter binding but not 5-HT content, unlike 3,4-methylenedioxyamethamphetamine
Journal name European journal of pharmacology   Check publisher's open access policy
ISSN 0014-2999
Publication date 2006-09-28
Sub-type Article (original research)
DOI 10.1016/j.ejphar.2006.07.011
Volume 546
Issue 1-3
Start page 74
End page 81
Total pages 8
Place of publication Netherlands
Publisher Elsevier
Language eng
Subject 111501 Basic Pharmacology
111506 Toxicology (incl.Clinical Toxicology)
110903 Central Nervous System
Abstract Worldwide growth in p-methoxyamphetamine (PMA) usage amongst ‘ecstasy’ users indicates a proportionally greater incidence of acute toxicity compared to 3,4-methylenedioxymethamphetamine (MDMA). While longer-term use of MDMA appears to produce degeneration of 5-hydroxytryptamine (5-HT, serotonin) neurons, PMA effects are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on two indices of 5-HT axonal degeneration, cortical brain 5-HT transporter (SERT) density and 5-HT/5-hydroxyindolacetic acid (5-HIAA) content. Treatment of male rats once daily for 4 days (10 or 20 mg/kg) with PMA or MDMA resulted in significant reductions (20 mg/kg: 53% and 23% of vehicle treatment respectively) in [3H]-paroxetine binding (SERT density) one week after final drug administration. When rats were housed at a higher ambient temperature (28 °C vs. 22 °C) for 6 h after dosing, no additive effect was seen for either drug. A more intensive dosing regimen (10 or 20 mg/kg twice daily for 4 days) was used to examine PMA/MDMA effects on cortical 5-HT content. Two weeks after MDMA treatment, significant reductions in cortical 5-HT content (20 mg/kg: 39% of vehicle treatment) were seen. However, PMA did not alter cortical 5-HT content, yet reduced cortical 5-HIAA content (20 mg/kg: 72% of vehicle treatment). These data suggest PMA has severe long-term implications clinically for alteration of 5-HT neurotransmission that may differ from MDMA, but may not necessarily be interpreted as a degeneration of 5-HT fibres.
Keyword Para-methoxyamphetamine
3,4-methylenedioxymethamphetamine
Serotonin transporter
Neurodegeneration
5-HT
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