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Previous issue date: 2017-08-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The social recognition memory (SRM) is crucial to reproduction, formation of social
groups and species survival. It is well known that oxytocin, vasopressin, sexual
hormones and the olfactory bulb are strongly involved in the formation of SEM. Despite
its relevance, the involvement of neurotransmitters such as dopamine (DA),
noradrenaline (NE) and histamine (HIS), as well as the brain structures basolateral
amygdala (BLA) and CA1 region of dorsal hippocampus ? commonly known for their
importance in consolidating and maintaining other types of memories ? remains
unknown when concerning SRM. Therefore, the first part of this study aims to evaluate
the participation of the D1/D5 dopaminergic, ?-adrenergic and H2 histaminergic
receptors into BLA and CA1 on consolidation of SRM. For this, male Wistar adult rats
(3 months) were submitted to the social discrimination task (SDT), which is based on
the natural tendency of the rodents to explore the novelty. The adult animal was
exposed to a juvenile (21 days) conspecific for 1 hour (training session) and 24 hours
later to the juvenile previously met (familiar) and to a new juvenile during 5 minutes
(test session), when the exploration time was measured. Pharmacological
interventions took place immediately after the training session. We verified that the H2
histaminergic receptors are required to the consolidation of SRM both in CA1 and BLA.
However, the activation of D1/D5 dopaminergic and ?-adrenergic receptors interferes
in an opposite way in the two brain structures: D1/D5 receptors are required in CA1,
but not in BLA for consolidation of MRS, whereas activation of ?-adrenergic receptors
is indispensable in BLA, but not in CA1. Methylphenidate (MPH) is a drug widely used
in the treatment of Attention Deficit Hyperactivity Disorder. It exerts its therapeutic
effect by increasing levels of DA and NE in brain structures involved in the learning
processes, such as prefrontal cortex (PFC) and hippocampus. Since DA and NE have
opposite actions in MRS, we decided to evaluate the effect of MPH on the formation
and recall of MRS, since this drug acts on the levels of both neurotransmitters and has
been used for academic doping by healthy individuals. Using SDT, with
pharmacological interventions at different times, we verified that: 1) MPH, administered
acutely prior to the information acquisition, blocked SRM; 2) Blockade was reversed
when the animals received MPH at the time of acquisition and retrieval, characterizing
the phenomenon known as state dependency (SD) learning; 3) The SD is associated
to the CPF, but not to CA1; 4) SD does not depend on CA1, since the increase of NE
in CA1 impairs the retrieval of the SRM. In addition, we verified that the 21-day chronic
treatment with MPH causes a greater persistence of MRS when a weaker training
session is performed. Considering the obtained results, this work demonstrates that
the hippocampus, the basolateral amygdala and the prefrontal cortex, modulated by
the dopaminergic and noradrenergic systems, regulate the SRM processing. / A mem?ria de reconhecimento social (MRS) ? crucial ? reprodu??o, forma??o de
grupos sociais e sobreviv?ncia das esp?cies. Sabe-se que a ocitocina, a
vasopressina, os horm?nios sexuais e o bulbo olfat?rio t?m um forte envolvimento na
forma??o da MRS. Apesar de sua relev?ncia, a participa??o de neurotransmissores,
como dopamina (DA), noradrenalina (NA) e histamina (HIS), bem como das estruturas
am?gdala basolateral (BLA) e regi?o CA1 do hipocampo (CA1) ? j? amplamente
conhecidos pela sua import?ncia na consolida??o e manuten??o de outros tipos de
mem?rias ? permanece desconhecido quanto ? MRS. Sendo assim, a primeira parte
deste trabalho buscou avaliar a participa??o dos receptores D1/D5 dopamin?rgicos,
?-adren?rgicos e H2 histamin?rgicos na BLA e CA1 sobre a consolida??o da MRS.
Para isso, ratos Wistar machos adultos (3 meses) foram submetidos a tarefa de
discrimina??o social (TDS), que baseia-se na tend?ncia natural dos roedores de
explorar a novidade. O animal adulto foi exposto a um juvenil (21 dias) coespec?fico
por 1 hora (sess?o de treino) e 24 horas depois ao juvenil previamente encontrado
(familiar) e a um novo juvenil durante 5 minutos (sess?o de teste), quando o tempo de
explora??o foi medido. As interven??es farmacol?gicas ocorreram imediatamente
ap?s a sess?o de treino. Verificou-se que os receptores H2 histamin?rgicos s?o
necess?rios para a consolida??o da mem?ria tanto em CA1 quanto na BLA. Contudo
a ativa??o dos receptores D1/D5 dopamin?rgicos e ?-adren?rgicos interfere de forma
oposta nas duas estruturas cerebrais: os receptores D1/D5 s?o necess?rios em CA1,
mas n?o na BLA para a consolida??o da MRS, enquanto a ativa??o dos receptores ?adren?rgicos
? indispens?vel na BLA, por?m n?o em CA1. O metilfenidato (MPH) ?
um f?rmaco amplamente utilizado no tratamento do Transtorno do D?ficit de Aten??o
e Hiperatividade. Exerce seu efeito terap?utico pelo aumento nos n?veis de DA e NA
em estruturas cerebrais envolvidas nos processos de aprendizagem, como c?rtex pr?frontal
(CPF) e hipocampo. Uma vez que a DA e a NA tem a??es opostas na MRS,
decidimos avaliar o efeito do MPH sobre a forma??o e a evoca??o da MRS, j? que
esta droga atua sobre os n?veis de ambos os neurotransmissores e tem sido utilizada
como doping acad?mico por indiv?duos saud?veis. Utilizando a TDS, com as
interven??es farmacol?gicas em diferentes momentos, verificamos que: 1) o MPH,
administrado de forma sist?mica aguda previamente ? aquisi??o da informa??o,
bloqueou a MRS; 2) O bloqueio foi revertido quando os animais receberam MPH no
momento da aquisi??o e da evoca??o, caracterizando o fen?meno conhecido como
depend?ncia de estado (DE); 3) A DE ? associada ao CPF, mas n?o a CA1; 4) A DE
n?o depende de CA1, pois o aumento de NA em CA1 prejudica a evoca??o da MRS.
Al?m disso, verificamos que o tratamento cr?nico de 21 dias com MPH causa uma
maior persist?ncia da MRS, quando realizada uma sess?o de treino mais fraca.
Considerando os resultados obtidos, este trabalho demonstra que o hipocampo, a
am?gdala basolateral e o c?rtex pr?-frontal, modulados pelos sistemas dopamin?rgico
e noradren?rgico, regulam o processamento da MRS.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/7792 |
| Date | 31 August 2017 |
| Creators | Zinn, Carolina Garrido |
| Contributors | Izquierdo, Ivan Antonio, Myskiw, Jociane de Carvalho |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, Brasil, Escola de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7620745074616285884, 500, 500, 500, 600, -224747486637135387, -969369452308786627, 2075167498588264571 |
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