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.
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.
authors.affiliation: Discipline of Pharmacology, School of Medical Sciences, Medical School North, The University of Adelaide, Adelaide, South Australia, 5005, Australia.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Callaghan
authors.forename: Kirsten
authors.initials: K
authors.lastname: Farrand
authors.forename: Abdallah
authors.initials: A
authors.lastname: Salem
authors.forename: Patrick
authors.initials: P
authors.lastname: Hughes
authors.forename: Lynette C
authors.initials: LC
authors.lastname: Daws
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Irvine
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000662:Amphetamines / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D006213:Hallucinogens / Q000378:metabolism / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism / Q000494:pharmacology*; D017374:Paroxetine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D000662:Amphetamines; D004298:Dopamine; D006213:Hallucinogens; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017374:Paroxetine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C100230:4-methoxyamphetamine