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
| Autor: | Rodney J. Irvine, Lynette C. Daws, Patrick A. Hughes, Abdallah Salem, Paul D. Callaghan, Kirsten Farrand |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Serotonin Time Factors Dopamine N-Methyl-3 4-methylenedioxyamphetamine Ecstasy Pharmacology Binding Competitive Synaptic Transmission Rats Sprague-Dawley chemistry.chemical_compound medicine Electrochemistry Animals Neurotransmitter 5-HT receptor Serotonin transporter Chromatography High Pressure Liquid para-Methoxyamphetamine Brain Chemistry Cerebral Cortex Serotonin Plasma Membrane Transport Proteins biology Dose-Response Relationship Drug Amphetamines MDMA Hydroxyindoleacetic Acid Acute toxicity Rats Paroxetine chemistry biology.protein Hallucinogens 3 4-Dihydroxyphenylacetic Acid Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | European journal of pharmacology. 546(1-3) |
| ISSN: | 0014-2999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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