TY - JOUR
T1 - 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
AU - Callaghan, Paul D.
AU - Farrand, Kirsten
AU - Salem, Abdallah
AU - Hughes, Patrick
AU - Daws, Lynette C.
AU - Irvine, Rodney J.
N1 - Funding Information:
This study was supported by funding from the NHMRC to RJI and an Australian Postgraduate Award to PDC.
PY - 2006/9/28
Y1 - 2006/9/28
N2 - 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.
AB - 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.
KW - 3,4-methylenedioxymethamphetamine
KW - 5-HT
KW - Neurodegeneration
KW - Para-methoxyamphetamine
KW - Serotonin transporter
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U2 - 10.1016/j.ejphar.2006.07.011
DO - 10.1016/j.ejphar.2006.07.011
M3 - Article
C2 - 16925993
AN - SCOPUS:33748295675
VL - 546
SP - 74
EP - 81
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -