Elevated BDNF protein level in cortex but not in hippocampus of MDMA-treated Dark Agouti rats: a potential link to the long-term recovery of serotonergic axons.
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to cause selective long-term serotonergic damage. In this study, we examined the pattern of BDNF protein expression 1 day, 3, 8, 12 and 24 weeks after a single 15mg/kg i.p. dose of MDMA to adolescent Dark Agouti rats. In parallel, we measured either tryptophan-hydroxylase immunoreactive (TpH IR) axon density, or [(3)H]-paroxetine-binding in parietal cortex and hippocampus, two brain areas known to have different recovery capacity after MDMA, to test whether BDNF-levels were associated with the long-term recovery of serotonergic fibers after a neurotoxic dose of MDMA. Both TpH IR axon density and [(3)H]-paroxetine-binding were significantly decreased 3 weeks after the treatment in both brain areas but while normalization in both parameters was found in parietal cortex 24 weeks after treatment, significant decreases remained evident in the hippocampus. In the parietal cortex, a significant reduction in BDNF protein levels was found in the acute phase after treatment (1 day), which was followed by a robust increase 8 weeks later and a return to control levels by 12 weeks. In contrast, no significant alteration of BDNF protein level was found in the hippocampus at any time points. This absence of any significant increase in BDNF protein levels in the hippocampus, and the persistence in this region of decreases in TpH IR axon density and [(3)H]-paroxetine-binding, raises the possibility that BDNF has an important role in the long-term recovery of serotonergic axons after MDMA treatment.
Adori
Csaba
C
Department of Pharmacodynamics, Semmelweis University, Budapest H-1089, Hungary.
Andó
Rómeó D
RD
Ferrington
Linda
L
Szekeres
Mária
M
Vas
Szilvia
S
Kelly
Paul A T
PA
Hunyady
László
L
Bagdy
György
G
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013287:Illicit Drugs / Q000633:toxicity*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D010296:Parietal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017374:Paroxetine / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D013287:Illicit Drugs; D012701:Serotonin; D017374:Paroxetine; D014365:Tryptophan Hydroxylase; D018817:N-Methyl-3,4-methylenedioxyamphetamine