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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2017.tde-13072017-124411
Document
Author
Full name
Maria Cristina Valzachi Rocha Maluf
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Camarini, Rosana (President)
Bernardi, Maria Martha
Cruz, Fábio Cardoso
Felicio, Luciano Freitas
Joselevitch, Christina
Title in Portuguese
Estudo das vias de ativação do CREB na neuroplasticidade induzida por cocaína em camundongos adolescentes e adultos.
Keywords in Portuguese
Adolescentes
Camundongos
Cocaína
Expressão gênica
Proteínas
Sensibilização
Abstract in Portuguese
A fase da adolescência difere da adulta em parâmetros comportamentais e neurológicos. A proteína de ligação responsiva ao AMPc (CREB) é um fator de transcrição regulado por três vias principais: PKA, CaMK e ERK, as quais apresentam atividade alterada em resposta à cocaína. Neste trabalho, foram avaliadas as atividades dessas vias, bem como os níveis de um de seus genes alvo (prodinorfina), do inibidor endógeno de CRE (Icer) e da proteína ativadora de CREB (CBP) em resposta à administração de cocaína, além dos comportamentos induzidos pelo psicoestimulante. Os adolescentes apresentaram maior sensibilização psicomotora, atividade exploratória e comportamento tipo ansiedade em comparação aos adultos. Os adolescentes exibiram aumento da atividade da via da PKA e da expressão de Icer, CBP e Pdyn; os adultos apresentaram diminuição de CaMKs, GluR1 e Icer. Essas diferentes respostas neuroadaptativas podem ajudar na compreensão dos mecanismos ontogênicos envolvidos na dependência.
Title in English
Study of the pathways of CREB activation in cocaine-induced neuroplasticity in adolescent and adult mice.
Keywords in English
Adolescents
Cocaine
Gene expression
Mice
Proteins
Sensitization
Abstract in English
The adolescence differs from adulthood in behavioral and neurochemichal aspects. The cAMP responsive binding protein (CREB) is a transcription factor regulated by three main pathways in the mesolimbic-dopaminergic circuit: PKA, CaMK and ERK, which are modulated by cocaine. This study evaluated the activity of these pathways, as well as the levels of one of its main target genes (prodynorphin), endogenous CRE inhibitor (Icer) and CREB binding protein (CBP) in response to cocaine administration, besides the behaviors induced by the psychostimulant. Adolescents presented greater locomotor activation, psychomotor sensitization, exploratory activity and anxiety-like behavior compared to adults. Adolescents exhibited increased PKA pathway activity and expression of Icer, CBP, and Pdyn; adults showed decreased levels of CaMKs, GluR1 and Icer. These different neuroadaptive responses may help understanding the ontogenic mechanisms involved in addiction.
 
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Publishing Date
2017-07-13
 
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