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In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function.
J Neurochem 2007; 100(3):617-27JN

Abstract

p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of 'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with marked changes in serotonergic neurotransmission, but the long-term effects of PMA are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on in vitro measures of neurodegeneration: serotonin (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2 weeks later indices of SERT function were measured. [(3)H]5-HT uptake into synaptosomes and [(3)H]cyanoimipramine binding to the SERT were significantly reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that in vitro measures of 5-HT axonal degeneration do not necessarily predict potential compensatory mechanisms that maintain SERT function under basal conditions.

Authors+Show Affiliations

Department of Physiology, The University of Texas Health Science Center at San Antonio, TX 78229-3900, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17181558

Citation

Callaghan, Paul D., et al. "In Vivo Analysis of Serotonin Clearance in Rat Hippocampus Reveals That Repeated Administration of P-methoxyamphetamine (PMA), but Not 3,4-methylenedioxymethamphetamine (MDMA), Leads to Long-lasting Deficits in Serotonin Transporter Function." Journal of Neurochemistry, vol. 100, no. 3, 2007, pp. 617-27.
Callaghan PD, Owens WA, Javors MA, et al. In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. J Neurochem. 2007;100(3):617-27.
Callaghan, P. D., Owens, W. A., Javors, M. A., Sanchez, T. A., Jones, D. J., Irvine, R. J., & Daws, L. C. (2007). In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. Journal of Neurochemistry, 100(3), pp. 617-27.
Callaghan PD, et al. In Vivo Analysis of Serotonin Clearance in Rat Hippocampus Reveals That Repeated Administration of P-methoxyamphetamine (PMA), but Not 3,4-methylenedioxymethamphetamine (MDMA), Leads to Long-lasting Deficits in Serotonin Transporter Function. J Neurochem. 2007;100(3):617-27. PubMed PMID: 17181558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. AU - Callaghan,Paul D, AU - Owens,W Anthony, AU - Javors,Martin A, AU - Sanchez,Teresa A, AU - Jones,David J, AU - Irvine,Rodney J, AU - Daws,Lynette C, Y1 - 2006/12/01/ PY - 2006/12/22/pubmed PY - 2007/3/21/medline PY - 2006/12/22/entrez SP - 617 EP - 27 JF - Journal of neurochemistry JO - J. Neurochem. VL - 100 IS - 3 N2 - p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of 'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with marked changes in serotonergic neurotransmission, but the long-term effects of PMA are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on in vitro measures of neurodegeneration: serotonin (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2 weeks later indices of SERT function were measured. [(3)H]5-HT uptake into synaptosomes and [(3)H]cyanoimipramine binding to the SERT were significantly reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that in vitro measures of 5-HT axonal degeneration do not necessarily predict potential compensatory mechanisms that maintain SERT function under basal conditions. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/17181558/In_vivo_analysis_of_serotonin_clearance_in_rat_hippocampus_reveals_that_repeated_administration_of_p_methoxyamphetamine__PMA__but_not_34_methylenedioxymethamphetamine__MDMA__leads_to_long_lasting_deficits_in_serotonin_transporter_function_ L2 - https://doi.org/10.1111/j.1471-4159.2006.04247.x DB - PRIME DP - Unbound Medicine ER -