Violent crime and aggressive behaviour are of increasing concern in New Zealand. Much of this is displayed by adolescent males who have an association with some form of substance use, abuse or dependence. This is especially relevant for stimulant drugs, especially methamphetamine (MA), and 1-benzylpiperazine (BZP). Previous research has shown that BZP has similar neurochemical and behavioural effects to MA, and there is a large volume of research showing an association between chronic MA use and aggression. In contrast to this, there has been little research into the consequences of a single administration of MA, which is often portrayed by the media as having the same detrimental effects as chronic use. The present study was designed to determine whether or not acute MA would induce aggressive behaviour in adolescent male hooded rats. In addition, the study also examined whether BZP had a similar effect to MA. Sixty male hooded rats aged between 41 to 50 postnatal days (PND), were utilised and divided into five groups of 12 rats each: saline; 1mg/kg (low dose) or 2mg/kg (high dose) MA; 10mg/kg (low dose) or 20mg/kg (high dose) BZP. The rats were tested using the resident/intruder test of aggression, consisting of eight measures of aggressive behaviour. The results suggested that, rats treated with either a low or high dose of MA or BZP were significantly less aggressive than saline-treated rats. There appeared to be little to distinguish between the two drugs in their effects on the responses recorded. It was concluded that an acute administration of either MA or BZP did not increase aggression, and thus did not support the view that aggression will result from a single dose of MA (or indeed BZP that has not been previously investigated in this context).

Vitamin A and its derivatives, known as retinoids, are involved in a number of functions in the developing and adult brain (Lane et al., 2005). Roaccutane (13-cis-retinoic acid, 13-cis-RA) is a synthetic retinoid used for the treatment of severe cystic acne, although its use has been controversially associated with adverse psychiatric events including depression. In this thesis, the presence of retinoid receptors in the rat hippocampus was verified and a similar profile of expression was observed in the rat raphe nuclei for the first time. The expression of retinoid receptors in brain regions that are implicitly associated with depression pathology provides proof of concept for retinoids to influence depressive behaviour. The ability of 13-cis-RA treatment to induce a pro-depressive profile in animal models of depression-related behaviour was tested. In the resident-intruder paradigm, adult rats treated for 7 or 14 days with 13-cis-RA (1mg/kg, i.p.) showed reduced aggressive behaviour, with a concomitant increase in flight submit and flight escape behaviours, compared with vehicle-treated controls. These findings are indicative of increased depression-related behaviour. However, chronic treatment did not alter depression-related behaviour in the forced swim test and sucrose consumption anhedonia paradigms The molecular mechanisms mediating 13-cis-RA-induced depression were investigated by examining monoaminergic gene expression, protein levels and neurotransmitter levels in rat brain tissue and plasma and an in vitro model. The majority of serotonergic components (SERT, 5-HT1AR, 5-HT1BR and MAOA) were not altered by chronic 13-cis-RA treatment, with the possible exception of TPH2 gene/protein expression and increased 5-HT levels in platelets. In fact, the expression of D2 dopamine receptor was significantly elevated in the RN46A-B14 cell line (10μM 13-cis-RA, 48 h) and was similarly elevated at the protein level in the juvenile rat hippocampus (1mg/kg/day, i.p., 6 weeks), suggesting dopaminergic pathways may be of importance. There was also a trend in the data to suggest that 13-cis-RA-treated juvenile rats may be more susceptible the molecular alterations than corresponding adult rats. xii

No description available.

O Canabidiol (CBD), principal composto não-psicotomimético da Cannabis sativa, possui diversas propriedades farmacológicas, incluindo a indução de efeitos tipoantidepressivos e ansiolíticos em roedores após administração sistêmica. O isolamento social aumenta comportamentos agressivos em camundongos, condição denominada agressão induzida pelo isolamento social ou agressão territorial. Drogas ansiolíticas e antidepressivas podem atenuar comportamentos agressivos. Desse modo, o objetivo do presente trabalho foi avaliar se o CBD atenuaria comportamentos agressivos induzidos pelo isolamento social em camundongos. Camundongos Suíços machos (7-8 semanas de idade no dia do isolamento, 30-40 g no dia do teste) foram mantidos isolados (camundongos residentes) para indução dos comportamentos agressivos. Paralelamente, camundongos co-específicos (camundongos intrusos) foram mantidos agrupados (oito por caixa). Neste modelo, um camundongo intruso da mesma linhagem, sexo e idade foi colocado na caixa moradia do residente. As interações entre os camundongos residente e intruso foram gravadas por 20 min e a latência para a primeira mordida contra o intruso, o número de ataques e o tempo total de ataques foram analisados por um observador cego aos grupos experimentais. Após 10 dias de isolamento social, foi testado se a administração aguda (i.p.) de CBD (5, 15, 30 ou 60 mg/kg), 30 min antes do teste, atenuaria comportamentos agressivos dos camundongos residentes contra os intrusos. Para avaliar a participação de receptores 5-HT1A e CB1 nos efeitos do CBD, grupos independentes de animais receberam 1 injeção prévia de WAY 100635 (antagonista dos receptores 5-HT1A, 0,3 mg/kg) ou AM251 (antagonista dos receptores CB1, 1 mg/kg), 30 min antes do CBD (15 mg/kg). Para controlar possíveis efeitos motores da droga, grupos independentes de animais tratados com doses efetivas de CBD ou não efetivas de WAY100635 ou AM251 foram submetidos ao actímetro para avaliação da atividade locomotora total. O CBD (15 mg/kg) aumentou a latência para o residente atacar o intruso e este efeito foi atenuado tanto pela administração prévia de AM251 (VEI+VEI: 186,62±83,16; VEI+CBD: 956,25±150,77; AM+VEI: 271,71±156,18; AM+CBD: 395,86±208,24; p=0,030) quanto WAY100635 (VEI+VEI: 116,33±29,38; VEI+CBD: 860,87±177,36; WAY+VEI: 305,12±159,16; WAY+CBD: 302,57±154,68; p=0,011). Além disso, o CBD reduziu o número de ataques em todas as doses testadas (VEI: 23,00±3,66; CBD 5: 12,25±2,43; CBD 15: 6,62±2,43; CBD 30: 7,71±3,24; CBD 60: 8,16±2,36; p=0,002) e as doses intermediárias (15 e 30 mg/kg) foram capazes de diminuir o tempo total de ataques (VEI: 114,37±22,65; CBD 5: 80,87±23,83; CBD 15: 40,00±14,58; CBD 30: 25,86±12,88; CBD 60: 54,67±9,68; p=0,018), ambos os efeitos sendo atenuados pelo AM251 (Número de ataques - VEI+VEI: 19,25±2,56; VEI+CBD: 3,25±2,36; AM+VEI: 22,86±4,97; AM+CBD: 14,14±4,10; p=0,028; Tempo total de ataques - VEI+VEI: 66,62±9,19; VEI+CBD: 11,75±9,56; AM+VEI: 118,86±31,00; AM+CBD: 58,71±17,45; p=0,049) e WAY100635 (Número de ataques - VEI+VEI: 30,83±6,77; VEI+CBD: 7,87±4,68; WAY+VEI: 22,50±5,06; WAY+CBD: 23,57±6,74; p=0,059; Tempo total de ataques - VEI+VEI: 151,17±32,65; VEI+CBD: 16,75±10,88; WAY+VEI: 113,75±24,66; WAY+CBD: 76,29±21,36; p=0,002). Não foi observado efeito motor do CBD em nenhuma das doses testadas, bem como do WAY100635 e AM251. Esses resultados evidenciam que o CBD atenua comportamentos agressivos em camundongos e nos permitem sugerir um mecanismo misto, visto que há o envolvimento de receptores CB1 e 5-HT1A. Desse modo, este fitocanabinoide poderia ser uma alternativa terapêutica para tratar comportamentos agressivos associados a transtornos psiquiátricos / Cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa plant, induces anxiolytic- and antidepressant-like effects in rodents after systemic administration. Long-term individual housing increases aggressive behavior in mice, a condition named isolation-induced aggression or territorial aggression, which can be attenuated by anxiolytic and antidepressant drugs. Thus, the aim of the present study was to verify whether CBD would attenuate the aggressive behavior induced by social isolation. Male Swiss mice (7-8 weeks of age on the isolation day, 30-40 g on the test day) were individually housed (resident mice) to induce aggressive behavior, while conspecific mice (intruder mice) were grouped housed (eight per cage). In this model, an intruder mouse of the same strain, sex and age is placed in the resident home cage. The resident-intruder interactions were videotaped for 20 min and the latency to the first bite against the intruder, the number of attacks and the total duration of aggressive encounters were recorded and later analyzed by an observer blind to the treatment groups. After 10 days of social isolation, we tested if acute intraperitoneal CBD administration (5, 15, 30 and 60 mg/kg) to the resident mice 30 min prior to the test would attenuate aggressive-like behavior towards the intruder animal. To evaluate the involvement of 5-HT1A and CB1 receptors in the CBD effects, independent groups of animals were injected with WAY100635 (0.3 mg/kg) or AM251(1 mg/kg) 30 min prior to CBD (15 mg/kg). To control possible motor effects, independent animals treated with effective doses of CBD or ineffective doses of WAY100635 or AM251 were submitted to the actimeter to evaluate the total locomotor activity. CBD (15 mg/kg) increased latency to attack the intruder and this effect was attenuated by the prior administration of AM251 (VEI+VEI: 186.62±83.16; VEI+CBD: 956.25±150.77; AM+VEI: 271.71±156.18; AM+CBD: 395.86±208.24; p=0.030) or WAY100635 (VEI+VEI: 116.33±29.38; VEI+CBD: 860.87±177.36; WAY+VEI: 305.12±159.16; WAY+CBD: 302.57±154.68; p=0.011). Moreover, CBD reduced the number of attacks in all tested doses (VEI: 23.00±3.66; CBD 5: 12.25±2.43; CBD 15: 6.62±2.43; CBD 30: 7.71±3.24; CBD 60: 8.16±2.36; p=0.002) as well as the duration of aggressive behavior encounters in the intermediary doses (15 and 30 mg/kg; VEI: 114.37±22.65; CBD 5: 80.87±23.83; CBD 15: 40.00±14.58; CBD 30: 25.86±12.88; CBD 60: 54.67±9.68; p=0.018), both effects were attenuated by AM251 (Number of attacks - VEI+VEI: 19.25±2.56; VEI+CBD: 3.25±2.36; AM+VEI: 22.86±4.97; AM+CBD: 14.14±4.10; p=0.028; Total time of attacks - VEI+VEI: 66.62±9.19; VEI+CBD: 11.75±9.56; AM+VEI: 118.86±31.00; AM+CBD: 58.71±17.45; p=0.049) and WAY100635 (Number of attacks - VEI+VEI: 30.83±6.77; VEI+CBD: 7.87±4.68; WAY+VEI: 22.50±5.06; WAY+CBD: 23.57±6.74; p=0.059; Total time of attacks - VEI+VEI: 151.17±32.65; VEI+CBD: 16.75±10.88; WAY+VEI: 113.75±24.66; WAY+CBD: 76.29±21.36; p=0.002). CBD, in all tested doses, as well as WAY100635 and AM251, did not induce locomotor changes. These findings suggest that CBD decreases aggressive behaviors in mice and allow us to suggest that this effect involves CB1 and 5-HT1A receptors. Therefore, this phytocannabinoid may be therapeutically useful to treat aggressive behaviors that are usually associated with psychiatric disorders

O Canabidiol (CBD), principal composto não-psicotomimético da Cannabis sativa, possui diversas propriedades farmacológicas, incluindo a indução de efeitos tipoantidepressivos e ansiolíticos em roedores após administração sistêmica. O isolamento social aumenta comportamentos agressivos em camundongos, condição denominada agressão induzida pelo isolamento social ou agressão territorial. Drogas ansiolíticas e antidepressivas podem atenuar comportamentos agressivos. Desse modo, o objetivo do presente trabalho foi avaliar se o CBD atenuaria comportamentos agressivos induzidos pelo isolamento social em camundongos. Camundongos Suíços machos (7-8 semanas de idade no dia do isolamento, 30-40 g no dia do teste) foram mantidos isolados (camundongos residentes) para indução dos comportamentos agressivos. Paralelamente, camundongos co-específicos (camundongos intrusos) foram mantidos agrupados (oito por caixa). Neste modelo, um camundongo intruso da mesma linhagem, sexo e idade foi colocado na caixa moradia do residente. As interações entre os camundongos residente e intruso foram gravadas por 20 min e a latência para a primeira mordida contra o intruso, o número de ataques e o tempo total de ataques foram analisados por um observador cego aos grupos experimentais. Após 10 dias de isolamento social, foi testado se a administração aguda (i.p.) de CBD (5, 15, 30 ou 60 mg/kg), 30 min antes do teste, atenuaria comportamentos agressivos dos camundongos residentes contra os intrusos. Para avaliar a participação de receptores 5-HT1A e CB1 nos efeitos do CBD, grupos independentes de animais receberam 1 injeção prévia de WAY 100635 (antagonista dos receptores 5-HT1A, 0,3 mg/kg) ou AM251 (antagonista dos receptores CB1, 1 mg/kg), 30 min antes do CBD (15 mg/kg). Para controlar possíveis efeitos motores da droga, grupos independentes de animais tratados com doses efetivas de CBD ou não efetivas de WAY100635 ou AM251 foram submetidos ao actímetro para avaliação da atividade locomotora total. O CBD (15 mg/kg) aumentou a latência para o residente atacar o intruso e este efeito foi atenuado tanto pela administração prévia de AM251 (VEI+VEI: 186,62±83,16; VEI+CBD: 956,25±150,77; AM+VEI: 271,71±156,18; AM+CBD: 395,86±208,24; p=0,030) quanto WAY100635 (VEI+VEI: 116,33±29,38; VEI+CBD: 860,87±177,36; WAY+VEI: 305,12±159,16; WAY+CBD: 302,57±154,68; p=0,011). Além disso, o CBD reduziu o número de ataques em todas as doses testadas (VEI: 23,00±3,66; CBD 5: 12,25±2,43; CBD 15: 6,62±2,43; CBD 30: 7,71±3,24; CBD 60: 8,16±2,36; p=0,002) e as doses intermediárias (15 e 30 mg/kg) foram capazes de diminuir o tempo total de ataques (VEI: 114,37±22,65; CBD 5: 80,87±23,83; CBD 15: 40,00±14,58; CBD 30: 25,86±12,88; CBD 60: 54,67±9,68; p=0,018), ambos os efeitos sendo atenuados pelo AM251 (Número de ataques - VEI+VEI: 19,25±2,56; VEI+CBD: 3,25±2,36; AM+VEI: 22,86±4,97; AM+CBD: 14,14±4,10; p=0,028; Tempo total de ataques - VEI+VEI: 66,62±9,19; VEI+CBD: 11,75±9,56; AM+VEI: 118,86±31,00; AM+CBD: 58,71±17,45; p=0,049) e WAY100635 (Número de ataques - VEI+VEI: 30,83±6,77; VEI+CBD: 7,87±4,68; WAY+VEI: 22,50±5,06; WAY+CBD: 23,57±6,74; p=0,059; Tempo total de ataques - VEI+VEI: 151,17±32,65; VEI+CBD: 16,75±10,88; WAY+VEI: 113,75±24,66; WAY+CBD: 76,29±21,36; p=0,002). Não foi observado efeito motor do CBD em nenhuma das doses testadas, bem como do WAY100635 e AM251. Esses resultados evidenciam que o CBD atenua comportamentos agressivos em camundongos e nos permitem sugerir um mecanismo misto, visto que há o envolvimento de receptores CB1 e 5-HT1A. Desse modo, este fitocanabinoide poderia ser uma alternativa terapêutica para tratar comportamentos agressivos associados a transtornos psiquiátricos / Cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa plant, induces anxiolytic- and antidepressant-like effects in rodents after systemic administration. Long-term individual housing increases aggressive behavior in mice, a condition named isolation-induced aggression or territorial aggression, which can be attenuated by anxiolytic and antidepressant drugs. Thus, the aim of the present study was to verify whether CBD would attenuate the aggressive behavior induced by social isolation. Male Swiss mice (7-8 weeks of age on the isolation day, 30-40 g on the test day) were individually housed (resident mice) to induce aggressive behavior, while conspecific mice (intruder mice) were grouped housed (eight per cage). In this model, an intruder mouse of the same strain, sex and age is placed in the resident home cage. The resident-intruder interactions were videotaped for 20 min and the latency to the first bite against the intruder, the number of attacks and the total duration of aggressive encounters were recorded and later analyzed by an observer blind to the treatment groups. After 10 days of social isolation, we tested if acute intraperitoneal CBD administration (5, 15, 30 and 60 mg/kg) to the resident mice 30 min prior to the test would attenuate aggressive-like behavior towards the intruder animal. To evaluate the involvement of 5-HT1A and CB1 receptors in the CBD effects, independent groups of animals were injected with WAY100635 (0.3 mg/kg) or AM251(1 mg/kg) 30 min prior to CBD (15 mg/kg). To control possible motor effects, independent animals treated with effective doses of CBD or ineffective doses of WAY100635 or AM251 were submitted to the actimeter to evaluate the total locomotor activity. CBD (15 mg/kg) increased latency to attack the intruder and this effect was attenuated by the prior administration of AM251 (VEI+VEI: 186.62±83.16; VEI+CBD: 956.25±150.77; AM+VEI: 271.71±156.18; AM+CBD: 395.86±208.24; p=0.030) or WAY100635 (VEI+VEI: 116.33±29.38; VEI+CBD: 860.87±177.36; WAY+VEI: 305.12±159.16; WAY+CBD: 302.57±154.68; p=0.011). Moreover, CBD reduced the number of attacks in all tested doses (VEI: 23.00±3.66; CBD 5: 12.25±2.43; CBD 15: 6.62±2.43; CBD 30: 7.71±3.24; CBD 60: 8.16±2.36; p=0.002) as well as the duration of aggressive behavior encounters in the intermediary doses (15 and 30 mg/kg; VEI: 114.37±22.65; CBD 5: 80.87±23.83; CBD 15: 40.00±14.58; CBD 30: 25.86±12.88; CBD 60: 54.67±9.68; p=0.018), both effects were attenuated by AM251 (Number of attacks - VEI+VEI: 19.25±2.56; VEI+CBD: 3.25±2.36; AM+VEI: 22.86±4.97; AM+CBD: 14.14±4.10; p=0.028; Total time of attacks - VEI+VEI: 66.62±9.19; VEI+CBD: 11.75±9.56; AM+VEI: 118.86±31.00; AM+CBD: 58.71±17.45; p=0.049) and WAY100635 (Number of attacks - VEI+VEI: 30.83±6.77; VEI+CBD: 7.87±4.68; WAY+VEI: 22.50±5.06; WAY+CBD: 23.57±6.74; p=0.059; Total time of attacks - VEI+VEI: 151.17±32.65; VEI+CBD: 16.75±10.88; WAY+VEI: 113.75±24.66; WAY+CBD: 76.29±21.36; p=0.002). CBD, in all tested doses, as well as WAY100635 and AM251, did not induce locomotor changes. These findings suggest that CBD decreases aggressive behaviors in mice and allow us to suggest that this effect involves CB1 and 5-HT1A receptors. Therefore, this phytocannabinoid may be therapeutically useful to treat aggressive behaviors that are usually associated with psychiatric disorders

Benzodiazepines are widely abused by anxious individuals. Consequently, this thesis modeled anxiety in a mouse model in order to investigate benzodiazepine motivation within this sub-population. Using the Tube test of Social Dominance and the Resident/Intruder Paradigm I investigated whether animals identified as dominant or submissive/defeated would differentially display a preference for 0.25 mg/kg midazolam in a conditioned place preference paradigm. Consistent with my hypotheses, benzodiazepine preference was mediated by negative reinforcement as submissive but not dominant mice displayed a preference for midazolam. Furthermore, different neural systems mediated benzodiazepine preference dependent on the stress status of the animal (acute vs. chronic stress) such that, acutely stressed animals experienced benzodiazepine preference through a dopamine-independent pathway whereas chronically stressed animals experienced benzodiazepine preference through a dopamine-dependent pathway. Within chronically stressed mice, blockade of either D1 or D2 receptors attenuated benzodiazepine preference.

Benzodiazepines are widely abused by anxious individuals. Consequently, this thesis modeled anxiety in a mouse model in order to investigate benzodiazepine motivation within this sub-population. Using the Tube test of Social Dominance and the Resident/Intruder Paradigm I investigated whether animals identified as dominant or submissive/defeated would differentially display a preference for 0.25 mg/kg midazolam in a conditioned place preference paradigm. Consistent with my hypotheses, benzodiazepine preference was mediated by negative reinforcement as submissive but not dominant mice displayed a preference for midazolam. Furthermore, different neural systems mediated benzodiazepine preference dependent on the stress status of the animal (acute vs. chronic stress) such that, acutely stressed animals experienced benzodiazepine preference through a dopamine-independent pathway whereas chronically stressed animals experienced benzodiazepine preference through a dopamine-dependent pathway. Within chronically stressed mice, blockade of either D1 or D2 receptors attenuated benzodiazepine preference.

Etologicamente, os animais expressam repostas de medo frente a um predador ou a um co-especifico e a organização neural de respostas defensivas intraespecíficas são pouco conhecidas. Assim, o objetivo deste trabalho foi estudar o papel hipotalâmico na organização da defesa intraespecífica. Observamos que o núcleo pré-mamilar dorsal do hipotálamo também está ativo durante nesse tipo de defesa, porém porções distintas do mesmo. A lesão desse núcleo em ratos expostos a derrota social levou a importantes alterações comportamentais, praticamente abolindo comportamentos de defesa passiva. Notamos que regiões do hipotálamo lateral são as principais projeções aferentes do núcleo pré-mamilar dorsal e o principal alvo eferente é a coluna dorsomedial da matéria cinzenta periaquedutal. Concluímos que o hipotálamo é fundamental para a organização da defesa intraespecífica e que comportamentos defensivos inter e intra-específicos se utilizam de caminhos neurais distintos. / In nature, animals express fear responses toward a predator or a co-specific and not much is known about the neural organization of intra-specific defense. Therefore, the aim of this work was to analyze the role that the hypothalamus plays during the intra-specific defense expression. We observed that the dorsal premammilary nucleus is also mobilized during the agonistic encounter, but a different portion. Dorsal premammilary nucleus lesioned intruders led to important defense alterations, almost abolishing passive forms of defensive behavior. Notably, regions in lateral hypothalamus are particularly important for activating the dorsal premammilary nucleus and its efferent projection to the dorsomedial column of periaqueductal gray matter is the most important outcome for the defensive behavior expression. Concluding, the hypothalamus is fundamental for the neural organization of intra-specific defense and inter and intra-specific defensive behaviors are organized by distinct neural pathways.

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.

Etologicamente, os animais expressam repostas de medo frente a um predador ou a um co-especifico e a organização neural de respostas defensivas intraespecíficas são pouco conhecidas. Assim, o objetivo deste trabalho foi estudar o papel hipotalâmico na organização da defesa intraespecífica. Observamos que o núcleo pré-mamilar dorsal do hipotálamo também está ativo durante nesse tipo de defesa, porém porções distintas do mesmo. A lesão desse núcleo em ratos expostos a derrota social levou a importantes alterações comportamentais, praticamente abolindo comportamentos de defesa passiva. Notamos que regiões do hipotálamo lateral são as principais projeções aferentes do núcleo pré-mamilar dorsal e o principal alvo eferente é a coluna dorsomedial da matéria cinzenta periaquedutal. Concluímos que o hipotálamo é fundamental para a organização da defesa intraespecífica e que comportamentos defensivos inter e intra-específicos se utilizam de caminhos neurais distintos. / In nature, animals express fear responses toward a predator or a co-specific and not much is known about the neural organization of intra-specific defense. Therefore, the aim of this work was to analyze the role that the hypothalamus plays during the intra-specific defense expression. We observed that the dorsal premammilary nucleus is also mobilized during the agonistic encounter, but a different portion. Dorsal premammilary nucleus lesioned intruders led to important defense alterations, almost abolishing passive forms of defensive behavior. Notably, regions in lateral hypothalamus are particularly important for activating the dorsal premammilary nucleus and its efferent projection to the dorsomedial column of periaqueductal gray matter is the most important outcome for the defensive behavior expression. Concluding, the hypothalamus is fundamental for the neural organization of intra-specific defense and inter and intra-specific defensive behaviors are organized by distinct neural pathways.