This thesis investigates estrogens' modulation of three aspects of social cognition (aggression and agonistic behaviour, social learning, and social recognition). Sex-typical agonistic behaviour (males: overt attacks, females: more subtle dominance behaviours) was increased in gonadectomized mice by estrogen receptor alpha (ERα) agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), while non-overt agonistic behaviour was increased in male and female gonadally intact mice by ERβ agonist 7-Bromo-2-(4-hydroxyphenyl)-1,3-benzoxazol-5-ol (WAY-200070). Estrogens also affected the social transmission of food preferences (STFP). Acute estrogen and ERβ agonists WAY-200070 and 2,3-bis(4-hydroxyphenyl)propionitrile (DPN) prolonged the preference for the demonstrated food when administered pre-acquisition, likely by affecting motivation or the nature of the social interaction, while acute PPT blocked the STFP. All mice receiving any of the three treatments chronically showed a prolonged demonstrated food preference, suggesting a loss of ER specificity. Individual differences in social recognition may relate to increased oxytocin (OT) and vasopressin (AVP) mRNA, and ERα and ERβ gene activation, in the medial preoptic area, and decreased mRNA for ERs, OT receptor (OTR), AVP and AVP receptors 1a and 1b in the lateral amygdala. Additionally, dorsolateral septum ERs, progesterone receptor, and OTR may relate to social interest without affecting social recognition. Our and others' results suggest that estrogens, OT and AVP are all involved in social behaviours and mediate social recognition, social learning, social interactions, and aggression. ERs differently modulate the two types of social learning investigated here: ERα is critical for social recognition, but impairs social learning, while ERβ is less important in social recognition, and prolongs the demonstrated food preference in the STFP. This may be due to differences in receptor brain distributions or in downstream neurochemical systems that mediate these behaviours. The results of this thesis suggest that estrogens, through the various systems they modulate, have a key role to play in social behaviour. Further investigations of how estrogens effect change in these systems at the molecular and cellular level, as well as the critical brain areas and downstream effectors involved in these complex behaviours, are needed, and could contribute to therapeutic interventions in socially-based, sexually dimorphic disorders, like the autism spectrum disorders, and women receiving hormone replacement therapy for negative peri- or post-menopausal symptoms. / National Science and Engineering Research Council (PGS-D, CGS-M)

Os animais são expostos a diferentes situações que podem colocar em risco sua sobrevivência. Na natureza estas situações, em geral, eliciam medo e ou ansiedade. A agressão é um conjunto de comportamentos direcionados a um indivíduo co específico, ou não, que tem como objetivo a aquisição de recursos ou proteção em situações de risco à sobrevivência. Considerando a interação entre medo/ansiedade e agressividade, este trabalho teve como objetivo estudar se essas situações podem modificar o comportamento agressivo agressividade em camundongos. O propósito deste estudo foi investigar se a pre-exposição de camundongos a estímulos estressores incondicionados (campo aberto, labirinto em cruz elevado, exposição ao rato, exposição a odor de rato) e condicionados (choque nas patas) podem modular o futuro comportamento agressivo em camundongos. Para atingir esse objetivo, os animais foram previamente expostos a diferentes situações capazes de provocar um estado de ansiedade e/ou medo e posteriormente submetidos ao encontro agonístico (teste residente intruso). As alterações na reatividade emocional induzidas pelas variáveis independentes foram medidas usando a resposta de sobressalto potencializado pelo medo e a análise de vocalizações ultrassônicas. Devido à influência relevante da neurotransmissão de GABA na agressão, as mudanças comportamentais induzidas pelas variáveis utilizadas foram associadas com o benzodiazepínico diazepam. Os dados obtidos no presente estudo após análise mostrou que a pré-exposição de camundongos a situações aversivas que provocam medo e / ou ansiedade alteram o seu comportamento. / Aggression is defined as a behavioral repertoire mainly directed to a conspecific for acquisition of resources and protection. In this context, anxiety and fear-like behaviors is commonly triggered by these survivors situations. Since aggression and fear are highly correlated in the present study we investigated whether previous exposure to environmental unconditioned (rat presence and rat odor, open field and elevated plus-maze tests, foot-shocks) and conditioned aversive stimuli (fear-potentiated startle) can modulate future aggressive behavior in mice. To achieve this goal, the animals were previously exposed to different situations able to elicit a state of anxiety and/or fear and later submitted to the agonistic encounter. Changes on the emotional reactivity induced by the independent variables used were measured using the fear-potentiated startle response and ultrasonic vocalizations analysis. Due to the relevant influence of GABA neurotransmission on aggression, behavioral changes induced by the variables used were challenged with the prototypic benzodiazepine diazepam. In addition, regarding human aggression, the most effective and enduring pharmacological intervention rely on compounds that act as dopaminergic antagonists. Therefore, in our study, in order to verify the influence of dopamine neurotransmission on the modulation of aggression pharmacological manipulation was conducted with the systemic administration of the dopamine D2 agonist apomorphine. Both drugs were administered previously to the resident-intruder test. The data obtained in the present study after analysis show that the pre-exposure to aversive situations that trigger fear and/or anxiety changes mice behavior.