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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
Author(s) -
Callaghan Paul D.,
Owens W. Anthony,
Javors Martin A.,
Sanchez Teresa A.,
Jones David J.,
Irvine Rodney J.,
Daws Lynette C.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04247.x
Subject(s) - mdma , serotonergic , serotonin , serotonin transporter , in vivo , endocrinology , hippocampus , neurotransmitter , medicine , pharmacology , chemistry , biology , central nervous system , receptor , microbiology and biotechnology
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.