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.
From: Discipline of Pharmacology, School of Medical Sciences, Medical School North, The University of Adelaide, Adelaide, South Australia, 5005, Australia.
European journal of pharmacology
- Publish Date: Sep 2006
- ISSN: 0014-2999
- Volume: 546
- Issue: 1-3
- Pages: 74-81
- Medium: Print
- Language: English
- Citation (JAMA): Callaghan Paul D, Farrand Kirsten, Salem Abdallah, et al. 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.. Eur. J. Pharmacol. Sep 2006;546:74-81
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 [(3)H]-paroxetine binding (SERT density) one week after final drug administration. When rats were housed at a higher ambient temperature (28 degrees C vs. 22 degrees 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.
Mesh Headings (Keywords): 3,4-Dihydroxyphenylacetic Acid, Amphetamines, Animals, Binding, Competitive, Brain Chemistry, Cerebral Cortex, Chromatography, High Pressure Liquid, Dopamine, Dose-Response Relationship, Drug, Electrochemistry, Hallucinogens, Hydroxyindoleacetic Acid, Male, N-Methyl-3,4-methylenedioxyamphetamine, Paroxetine, Rats, Rats, Sprague-Dawley, Serotonin, Serotonin Plasma Membrane Transport Proteins, Serotonin Uptake Inhibitors, Synaptic Transmission, Time Factors
Check for Full Text / PubMed Unique Identifier (PMID): 16925993
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