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Long‐term impairment of anterograde axonal transport along fiber projections originating in the rostral raphe nuclei after treatment with fenfluramine or methylenedioxymethamphetamine
Author(s) -
Callahan Brian T.,
Cord Branden J.,
Ricaurte George A.
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1032
Subject(s) - fenfluramine , 5,7 dihydroxytryptamine , chemistry , raphe nuclei , raphe , neurotoxin , mdma , serotonin , serotonergic , forebrain , medial forebrain bundle , dorsal raphe nucleus , axoplasmic transport , endocrinology , medicine , neuroscience , pharmacology , biology , central nervous system , striatum , dopamine , biochemistry , receptor
To further evaluate the serotonin (5‐HT) neurotoxic potential of substituted amphetamines, we used tritiated proline to examine anterograde transport along ascending axonal projections originating in the rostral raphe nuclei of animals treated 3 weeks previously with (±)fenfluramine (FEN, 10 mg/kg, every 2 h × 4 injections; i.p.) or (±)3,4‐methylenedioxymethamphetamine (MDMA, 20 mg/kg, twice daily for 4 days; s.c.). The documented 5‐HT neurotoxin, 5,7‐dihydroxytryptamine (5,7‐DHT, 75 μg; ICV; 30 min after pretreatment with pargyline, 50 mg/kg; i.p., and desipramine 25 mg/kg; i.p.), served as a positive control. Along with anterograde axonal transport, we measured two 5‐HT axonal markers, 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA). Prior treatment with FEN or MDMA led to marked reductions in anterograde transport of labeled material to various forebrain regions known to receive 5‐HT innervation. These reductions were associated with lasting decrements in 5‐HT axonal markers. In general, decreases in axonal transport were less pronounced than those in 5‐HT and 5‐HIAA. However, identical changes were observed after 5,7‐DHT. These results further indicate that FEN and MDMA, like 5,7‐DHT, are 5‐HT neurotoxins. Synapse 40:113–121, 2001. © 2001 Wiley‐Liss, Inc.