Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2017-12-26T13:48:34Z No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-12-29T11:25:22Z (GMT) No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) / Made available in DSpace on 2017-12-29T11:48:08Z (GMT). No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) 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.