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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2020.tde-24012020-113021
Document
Author
Full name
Mariana Beu Rae
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Camarini, Rosana (President)
Garcia, Raphael Caio Tamborelli
Munhoz, Carolina Demarchi
Vialou, Vincent François Luc
Title in Portuguese
Estudo do enriquecimento ambiental na recompensa e na modulação do sistema de oxitocina.
Keywords in Portuguese
Dependência
Enriquecimento ambiental
Etanol
Interação social
Oxitocina
Abstract in Portuguese
A dependência tem como um dos fatores chaves a questão social. O enriquecimento ambiental (EA) promove aumento da interação social e apresenta efeitos positivos sobre a dependência. A OT (oxitocina) é responsável pela modulação da sociabilidade e está associada a manutenção do equilíbrio entre o valor recompensador do estímulo social e das drogas, corrompido durante a dependência. Camundongos Swiss machos adultos foram separados em dois grupos: controle (CT) e EA por 21 dias antes da realização dos testes. A interação e comportamento social avaliados pelos testes de Crawley e do tubo de dominância encontram-se aumentados no grupo EA, comparado com CT. A preferência condicionada a lugar foi adaptada e realizada com etanol vs estímulo social e revelou maior preferência pelo etanol no grupo EA e no grupo tratado com o análogo de OT, carbetocina. A motivação foi avaliada usando o teste de Food Enticing e revelou menor interação com alimento palatável nos animais enriquecidos. Por fim, a análise da expressão gênica através de qPCR mostrou que o EA promove aumento da expressão de OT e VP no hipotálamo e no estriado, respectivamente, além de diminuir a ativação de OTR no estriado, utilizando o ensaio de dosagem de PLC. Devido a semelhança estrutural entre os sistemas de OT e VP, foi realizado o teste de dosagem de Ca2+ para estudar a interação cruzada entre esses sistemas. A OT foi capaz de ativar receptores V1a com maior eficácia do que a VP ativando OTR. Finalmente, podemos concluir que o ambiente enriquecido é capaz de modular a interação social e a motivação dos animais e de aumentar a preferência pelo etanol frente a um estímulo social, além de modular a expressão gênica de oxitocina e vasopressina, que podem estar envolvidos com diferenças comportamentais observadas.
Title in English
Study of environmental enrichment on reward and modulation of the oxytocinergic system.
Keywords in English
Drug addiction
Environmental enrichment
Ethanol
Oxytocin
Social interaction
Abstract in English
Drug addiction presents sociability as a key point. Environmental enrichment (EE) promotes social interaction and shows protective effects upon drug abuse. Oxytocin (OT) is responsible for the modulation of sociability and is linked to the maintenance of the balance between the reward value of social and drug stimuli, which is corrupted during addiction. Male adults Swiss mice were separated in 2 groups: control (CT) and EE during 21 days before the following tests were performed. Here, social interaction and behavior, evaluated using Crawley test and social dominance tube test, were higher in enriched animals, compared to controls. Conditioned place preference test was modified and performed using alcohol vs social stimulus and showed higher preference for alcohol in EE animals and animals treated with an OT analogue, carbetocin. Motivation was explored through Food Enticing test, and reveled lower interaction with palatable food in enriched animals. Finally, gene expression analysis using qPCR revealed that EE promotes increase in expression of OT and VP in the hypothalamus and striatum, respectively, as well as decrease activation of OTR in the striatum, evaluated by using a PLC assay. Due to the similarities between OT and VP systems, Ca2+ release assay was used to study the cross-talk between both systems. OT was able to activate V1a with higher efficacy then VP activating OTR. Lastly, we were able to conclude that an enriched environment is capable of modulating social interaction, and motivation in animals and increase alcohol place preference over social preference, alongside modualting the increase of OT and VP , which could be involved with the behavioral changes observed.
 
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Release Date
2022-01-23
Publishing Date
2020-01-28
 
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