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Previous issue date: 2015-12-16 / Os objetivos desta tese foram os de investigar padr?es comportamentais e eletrofisiol?gicos associados
? resili?ncia e suscetibilidade ao estresse social induzido em camundongos. Para isso, utilizamos um
protocolo de indu??o de estresse cr?nico cont?nuo a partir de derrotas sociais baseado no paradigma
residente-intruso. Os resultados da tese s?o apresentados em dois estudos. No primeiro estudo,
camundongos C57BL/6J submetidos a epis?dios repetidos de derrota social apresentaram motiva??o
tardia para interagir com um camundongo desconhecido em sess?es prolongadas (10 min) do teste de
intera??o social. Utilizando uma abordagem etol?gica associada ? an?lise computacional de v?deos foi
poss?vel rastrear precisamente a posi??o dos camundongos durante a realiza??o de comportamentos de
investiga??o social. Analisamos ainda a express?o detalhada de comportamentos defensivos, tais como
investiga??o em postura estendida e fugas, ambos associados ao comportamento de investiga??o
social. A partir dessas an?lises demonstramos que a realiza??o do comportamento de investiga??o
social em postura estendida era significativamente maior para o grupo derrotado comparado ao grupo
controle. Ainda, um subgrupo de camundongos derrotados apresentou investiga??o social em postura
estendida de forma persistente e sem habitua??o. Utilizando uma medida da dist?ncia de investiga??o
durante as investiga??es sociais calculamos um ?ndice de aproxima??o (IA) para cada animal e
separamos um subgrupo apresentando fen?tipo relacionado ? ansiedade. A incid?ncia de fugas
tamb?m foi maior no grupo derrotado em compara??o com os controles. A persist?ncia na ocorr?ncia
desse comportamento foi observada em um subgrupo de camundongos submetidos ?s derrotas sociais.
Calculamos ent?o um ?ndice de fugas (IF) que se correlacionou inversamente com a prefer?ncia por
sacarose, sendo ?til para identificar animais aned?nicos. No segundo estudo, foram combinados
an?lise etol?gica e registros eletrofisiol?gicos com tetrodos na ?rea tegmentar ventral de camundongos
submetidos ? derrotas sociais. Utilizando crit?rios eletrofisiol?gicos e farmacol?gicos classificamos
unidades na ?rea tegmentar ventral como supostos neur?nios dopamin?rgicos e n?o-dopamin?rgicos.
Durante o comportamento de investiga??o social foi observado que a modula??o da taxa de disparo
dessas subpopula??es neuronais distintas ocorreu de maneira oposta em animais suscet?veis e
resilientes ao estresse social. Em suma, propomos que sess?es prolongadas associadas ? an?lise
etol?gica detalhada durante os testes de intera??o social podem prover informa??o para classifica??o
de camundongos em resilientes e suscept?veis ap?s repetidas derrotas sociais. Ainda, a express?o do
fen?tipo suscet?vel parece estar associada ao comprometimento do sistema dopamin?rgico
mesol?mbico na atribui??o de valor de incentivo ?s intera??es sociais normalmente associadas ao
aumento da atividade neuronal mesol?mbica. / The aims of this thesis were to investigate behavioral and electrophysiological patterns associated to
resilience and susceptibility to social stress in mice. For this, we used a chronic social defeat stress
protocol based on the resident-intruder paradigm. The results are presented here in two studies. In the
first study, C57BL/6J mice submitted to repeated social defeat episodes showed delayed motivation to
interact with an unfamiliar conspecific in long duration (10 min) sessions of the social interaction test.
By using an ethological approach combined with computational video analysis, it was possible to track
precisely the mouse position during social investigation behavior performance. With that approach, it
was analyzed the detailed expression of defensive behaviors, such as stretched attended postures and
flights, both associated to social investigation behaviors. From these analyzes, it was demonstrated
that social investigation behaviors based on stretched attend postures were significantly higher in
defeated mice in comparison to controls. Still, a subpopulation of defeated mice showed persistently
and non-habituating stretched attend postures during social investigation. By using a measure based on
the investigation distance during social investigations, it was possible to compute an approach index
(AI) to each animal and separate a subpopulation showing an anxiety-related phenotype. The flight
incidence was also increased in defeated group as compared with controls. The persistent occurrence
of this behavior was observed in a subpopulation of defeated mice. We calculated a flight index (FI)
that inversely correlated with sucrose preference, showing to be useful to identify anhedonic animals.
In the second study, we combined ethological approach and electrophysiological recordings in the
ventral tegmental area of mice submitted to chronic social defeat stress. By using electrophysiological
and pharmacological criteria, single-units recorded from the ventral tegmental area were classified as
putative dopaminergic and non-dopaminergic neurons. During the social investigation behavior it was
observed that firing rate modulations of distinct neuronal subpopulations occurred in opposite manner
in social defeat susceptible and resilient mice. In summary, this work proposes that longer sessions of
the social interaction test associated to ethological approach can provide information for the
behavioral classifications of resilient and susceptible mice after social defeat stress. Furthermore, the
expression of susceptible phenotype could be related to the midbrain dopaminergic system impairment
in the incentive value assignment to social interactions normally associated with increased mesolimbic
neuronal activity.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/21620 |
| Date | 16 December 2015 |
| Creators | Alves, Aron de Miranda Henriques |
| Contributors | 16256304845, http://lattes.cnpq.br/3384801391828521, Laplagne, Diego Andres, 70638083460, http://lattes.cnpq.br/0293416967746987, Quadros, Isabel Marian Hartmann de, 16501680808, http://lattes.cnpq.br/3982014468609862, Le?o, Richardson Naves, 99944251615, http://lattes.cnpq.br/0683942077872227, Figuerola, Wilfredo Blanco, 05579557779, http://lattes.cnpq.br/9912829629195282, Queiroz, Cl?udio Marcos Teixeira de |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM NEUROCI?NCIAS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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