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Serotonin Depletion Does not Modify the Short-Term Brain Hypometabolism and Hippocampal Neurodegeneration Induced by the Lithium–Pilocarpine Model of Status Epilepticus in Rats

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Abstract

It has been reported that fluoxetine, a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, has neuroprotective properties in the lithium–pilocarpine model of status epilepticus (SE) in rats. The aim of the present study was to investigate the effect of 5-HT depletion by short-term administration of p-chlorophenylalanine (PCPA), a specific tryptophan hydroxylase inhibitor, on the brain hypometabolism and neurodegeneration induced in the acute phase of this SE model. Our results show that 5-HT depletion did modify neither the brain basal metabolic activity nor the lithium–pilocarpine-induced hypometabolism when evaluated 3 days after the insult. In addition, hippocampal neurodegeneration and astrogliosis triggered by lithium–pilocarpine were not exacerbated by PCPA treatment. These findings point out that in the early latent phase of epileptogenesis, non-5-HT-mediated actions may contribute, at least in some extent, to the neuroprotective effects of fluoxetine in this model of SE.

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Acknowledgments

This work was financially supported by grants from the Spanish Ministerio de Ciencia e Innovación (SAF2009-09020) and Comunidad de Madrid (I2M2, S2010/BMD-2349). We are grateful to Dr. José Luis López-Lacomba, director of the Instituto de Estudios Biofuncionales UCM, and Dr. Enrique Martínez-Campos for kindly allowing us to use the fluorescence microscope.

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Authors and Affiliations

  1. Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII nº 1, 28040, Madrid, Spain

    Luis García-García, Ahmed Anis Shiha, Pablo Bascuñana, Javier de Cristóbal, Rubén Fernández de la Rosa, Mercedes Delgado & Miguel A. Pozo

  2. Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain

    Luis García-García & Mercedes Delgado

  3. Instituto Tecnológico PET, C/Manuel Bartolomé Cossío nº 10, 28040, Madrid, Spain

    Miguel A. Pozo

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  1. Luis García-García
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  2. Ahmed Anis Shiha
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  3. Pablo Bascuñana
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  4. Javier de Cristóbal
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  5. Rubén Fernández de la Rosa
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  6. Mercedes Delgado
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  7. Miguel A. Pozo
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Correspondence to Luis García-García.

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García-García, L., Shiha, A.A., Bascuñana, P. et al. Serotonin Depletion Does not Modify the Short-Term Brain Hypometabolism and Hippocampal Neurodegeneration Induced by the Lithium–Pilocarpine Model of Status Epilepticus in Rats. Cell Mol Neurobiol 36, 513–519 (2016). https://doi.org/10.1007/s10571-015-0240-4

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