Effective Neuroprotection of Acetyl-L-Carnitine over MDMA-Induced Serotonin loss in the Adoloscent Rat Brain
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1
IBMC– Instituto de Biologia Molecular e Celular, Neurobehaviour Unit, Portugal
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2
Universidade do Porto, Faculty of Pharmacy, Portugal
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3
NCTR/FDA, Division of Neurotoxicology, United States
3,4-Methylenedioximethamphetamine (MDMA) is a stimulant drug o abuse that induces persistent neurotoxic effects and onsets progressive neurodegenerative processes. The massive release of serotonin from pre- synaptic storage vesicles induced by MDMA followed by MAO-B metabolism, significantly increases oxidative stress at the mitochondrial level. L-carnitine and its ester, acetyl-L-carnitine (ALC), facilitate the transport of long chain free fatty acids across the mitochondrial membrane enhancing neuronal mitochondrial function. We have show that ALC exerts an effective neuroprotection against the MDMA-induced neurotoxicity at the mitochondrial level, reducing carbonyl formation, decreasing mtDNA deletion and improving the expression of the respiratory chain components. Here we evaluated the effects of ALC pre –administration on the serotonergic function it self. Adolescent male Wistar rats were assigned to four groups: control saline solution, isovolumetric to the MDMA solution, administered intraperitoneally (i.p.); MDMA (4x10mg/Kg MDMA, i.p.); ALC/MDMA (100mg/Kg 30 min of ALC prior to MDMA, i.p.) and ALC (100mg/Kg, i.p.). Rats were sacrificed two weeks after exposure and brains were dissected into: prefrontal cortex, striatum, hippocampus, amygdala, ventral mesencephalon (comprising the ventral tegmental area and substantia nigra, VTA/SN) and raphe nuclei. Levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were assessed by HPLC-EC. Analysis of the neurochemical data revealed a highly significant (p<0.001) protection of ALC treatment in the levels of 5-HT and 5-HIAA in all assessed brain regions The present work is the first to successfully demonstrate that a pretreatment with ALC is able to prevent the typical 5-HT loss that is induced in this model of neurotoxicity. These results indicate potential benefits of ALC application in the prevention and treatment of other neurodegenerative disorders induced by similar mechanisms of action.
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Neurodegenerative Disorders
Citation:
Alves
E,
Binienda
Z,
Carvalho
F,
Juliana Alves
C and
Summavielle
T
(2009). Effective Neuroprotection of Acetyl-L-Carnitine over MDMA-Induced Serotonin loss in the Adoloscent Rat Brain.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.098
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Received:
10 Aug 2009;
Published Online:
10 Aug 2009.
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Correspondence:
Teresa Summavielle, IBMC– Instituto de Biologia Molecular e Celular, Neurobehaviour Unit, Porto, Portugal, tsummavi@ibmc.up.pt