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Methylphenidate Restores Behavioral and Neuroplasticity Impairments in the Prenatal Nicotine Exposure Mouse Model of ADHD: Evidence for Involvement of AMPA Receptor Subunit Composition and Synaptic Spine Morphology in the Hippocampus.
Contreras, Darwin; Piña, Ricardo; Carvallo, Claudia; Godoy, Felipe; Ugarte, Gonzalo; Zeise, Marc; Rozas, Carlos; Morales, Bernardo.
Afiliação
  • Contreras D; Laboratory of Neuroscience, Faculty of Chemistry and Biology, University of Santiago de Chile, Alameda 3363, Santiago 9170022, Chile.
  • Piña R; Departamento de Biología, Facultad de Ciencias Básicas, Universidad Metropolitana de Ciencias de la Educación, Santiago 7760197, Chile.
  • Carvallo C; Departamento de Ciencias Pedagógicas, Facultad de Educación, Universidad Bernardo O'Higgins, Santiago 8370993, Chile.
  • Godoy F; Centro de investigación e innovación en Gerontología Aplicada (CIGAP), Facultad de Salud, Universidad Santo Tomás, Santiago 8370003, Chile.
  • Ugarte G; Laboratory of Neuroscience, Faculty of Chemistry and Biology, University of Santiago de Chile, Alameda 3363, Santiago 9170022, Chile.
  • Zeise M; Laboratory of Neuroscience, Faculty of Chemistry and Biology, University of Santiago de Chile, Alameda 3363, Santiago 9170022, Chile.
  • Rozas C; School of Psychology, Faculty of Humanities, University of Santiago de Chile, Santiago 9170022, Chile.
  • Morales B; Laboratory of Neuroscience, Faculty of Chemistry and Biology, University of Santiago de Chile, Alameda 3363, Santiago 9170022, Chile.
Int J Mol Sci ; 23(13)2022 Jun 26.
Article em En | MEDLINE | ID: mdl-35806103
ABSTRACT
In ADHD treatment, methylphenidate (MPH) is the most frequently used medication. The present work provides evidence that MPH restored behavioral impairments and neuroplasticity due to changes in AMPAR subunit composition and distribution, as well as maturation of dendritic spines, in a prenatal nicotine exposure (PNE) ADHD mouse model. PNE animals and controls were given a single oral dose of MPH (1 mg/kg), and their behavior was tested for attention, hyperactivity, and working memory. Long-term potentiation (LTP) was induced and analyzed at the CA3/CA1 synapse in hippocampal slices taken from the same animals tested behaviorally, measuring fEPSPs and whole-cell patch-clamp EPSCs. By applying crosslinking and Western blots, we estimated the LTP effects on AMPAR subunit composition and distribution. The density and types of dendritic spines were quantified by using the Golgi staining method. MPH completely restored the behavioral impairments of PNE mice. Reduced LTP and AMPA-receptor-mediated EPSCs were also restored. EPSC amplitudes were tightly correlated with numbers of GluA1/GluA1 AMPA receptors at the cell surface. Finally, we found a lower density of dendritic spines in hippocampal pyramidal neurons in PNE mice, with a higher fraction of thin-type immature spines and a lower fraction of mushroom mature spines; the latter effect was also reversed by MPH.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Metilfenidato Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Metilfenidato Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2022 Tipo de documento: Article