115 resultados para Núcleo dorsal da rafe

em Repositório Institucional UNESP - Universidade Estadual Paulista "Julio de Mesquita Filho"


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A lesão do núcleo mediano da rafe (NMR) produz sintomas que sugerem validade de face ao episódio maníaco. Esta pesquisa avaliou o efeito do lítio sobre a hiperatividade locomotora induzida por esta lesão. Vinte e um ratos Wistar machos foram submetidos à lesão eletrolítica da região do NMR (LR) e 17 foram submetidos à lesão fictícia (LF). Após recuperação, a atividade locomotora foi avaliada na caixa de atividade (Med Associates/ENV-515). Parte dos animais destes grupos recebeu tratamentos com lítio (47,5 mg/kg/2x dia i.p.) por 10 dias, enquanto o restante foi tratado com salina no mesmo esquema. A reavaliação ao final dos tratamentos demonstrou que o lítio reduziu significantemente a atividade locomotora em relação à avaliação inicial no grupo LR (ANOVA/Bonferroni p < 0,05), tornando-a equivalente aos baixos níveis dos grupos LF. Estes dados sustentam a hipótese de que as manifestações induzidas pela lesão do NMR podem constituir um modelo animal de mania.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Reações de defesa são respostas que os animais exibem diante de ameaças que podem comprometer sua integridade física ou a própria sobrevivência, tais como confrontos com o predador ou com animais da mesma espécie. O medo e a ansiedade são emoções que tem origem nestas reações, as quais envolvem respostas comportamentais e autonômicas e são acompanhadas da liberação de hormônios e neurotransmissores com função de preparar o organismo para responder àquela ameaça, seja fugindo ou enfrentando-a. Em se tratando da espécie humana, estas respostas defensivas eliciadas representariam a ocorrência de transtornos de ansiedade e, a busca por sua compreensão, resultou no desenvolvimento de modelos animais de ansiedade, dentre os quais se destaca o labirinto em cruz elevado (LCE), o qual se baseia na aversão natural de roedores a espaços abertos. Com relação aos substratos neurais envolvidos nestas manifestações, cabe destaque estruturas mesencefálicas, como a matéria cinzenta periaquedutal e núcleos da rafe, bem como prosencefálicas, como o complexo amidalóide e o córtex pré-frontal. O chamado complexo amidalóide ou amídala estendida compreende estruturas límbicas do prosencéfalo basal, incluindo-se o núcleo intersticial da estria terminal (do inglês: bed nucleus of stria terminalis, BNST) como uma área promissora no estudo da ansiedade. Uma variedade de neurotransmissores tem sido descrita como participante da mediação das respostas emocionais no BNST. Dentre eles, o chamado neurotransmissor atípico óxido nítrico (NO) tem sido investigado em diferentes estruturas cerebrais de roedores nas quais foram evidenciadas respostas pró-aversivas

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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No melhoramento genético de espécies florestais, uma população base ou indivíduos superiores pré-selecionados tem importância fundamental para a manutenção do programa. Indivíduos de melhores procedências e de ampla base genética propiciam a obtenção de ganhos de forma contínua. O objetivo deste trabalho foi avaliar a diversidade genética em duas populações-núcleo de Eucalyptus grandis. Foram avaliados 39 indivíduos, sendo 19 pertencentes à população 1 e 20, à população 2, utilizando-se 14 primers microssatélite. Os fragmentos foram identificados e analisados a partir dos programas GeneScan e Genotyper, utilizando-se um sequenciador automático ABI Prism 3100. O número de alelos encontrados para cada primer variou de cinco a 15 para a população 1 e, de 8 a 18 para a população 2. A heterozigosidade estimada foi maior na população 2, 0,869, contra 0,843 na população 1. A média da distância genética entre os indivíduos da população 1 foi 0,6220 e na população 2 foi 0,6112. Com a caracterização molecular dos indivíduos destas populações foi construído um banco de dados que permitirá, a partir dos parâmetros de genética de populações, monitorar esses programas de melhoramento em diferentes ciclos de seleção.

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It has been proposed that the ascending dorsal raphe (DR)-serotonergic (5-HT) pathway facilitates conditioned avoidance responses to potential or distal threat, while the DR-periventricular 5-HT pathway inhibits unconditioned flight reactions to proximal danger. Dysfunction on these pathways would be, respectively, related to generalized anxiety (GAD) and panic disorder (PD). To investigate this hypothesis, we microinjected into the rat DR the benzodiazepine inverse receptor agonist FG 7142, the 5-HT1A receptor agonist 8-OH-DPAT or the GABA(A) receptor agonist muscimol. Animals were evaluated in the elevated T-maze (ETM) and light/dark transition test. These models generate defensive responses that have been related to GAD and PD. Experiments were also conducted in the ETM 14 days after the selective lesion of DR serotonergic neurons by 5,7-dihydroxytriptamine (DHT). In all cases, rats were pre-exposed to one of the open arms of the ETM 1 day before testing. The results showed that FG 7142 facilitated inhibitory avoidance, an anxiogenic effect, while impairing one-way escape, an anxiolytic effect. 8-OH-DPAT, muscimol, and 5,7-DHT-induced lesions acted in the opposite direction, impairing inhibitory avoidance while facilitating one-way escape from the open arm. In the light/dark transition, 8-OH-DPAT and muscimol increased the time spent in the lighted compartment, an anxiolytic effect. The data supports the view that distinct DR-5-HT pathways regulate neural mechanisms underlying GAD and PD. (C) 2002 Elsevier B.V. B.V. All rights reserved.

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We evaluated the involvement of dorsal hippocampus (DH) 5-HT1A receptors in the mediation of the behavioral effects caused by the pharmacological manipulation of 5-HT neurons in the median raphe nucleus (MRN). To this end, we used the rat elevated T-maze test of anxiety. The results showed that intra-DH injection of the 5-HT1A/7 agonist 8-OH-DPAT facilitated inhibitory avoidance, an anxiogenic effect, without affecting escape. Microinjection of the 5-HT1A antagonist WAY-100635 was ineffective. In the elevated T-maze, inhibitory avoidance and escape have been related to generalized anxiety and panic disorders, respectively. Intra-MRN administration of the excitatory aminoacid kainic acid, which non-selectively stimulates 5-HT neurons in this brain area facilitated inhibitory avoidance and impaired escape performance, but also affected locomotion. Intra-MRN injection of WAY-100635, which has a disinhibitory effect on the activity of 5-HT neurons in this midbrain area, only facilitated inhibitory avoidance. Preadministration of WAY-100635 into the DH blocked the behavioral effect of intra-MRN injection of WAY-100635, but not of kainic acid. These results indicate that DH 5-HT1A receptors mediate the anxiogenic effect induced by the selective stimulation of 5-HT neurons in the MRN. (c) 2007 Elsevier B.V. and ECNP. All rights reserved.

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In order to investigate the relationship between behaviors elicited by chemical stimulation of the dorsal periaqueductal gray (dorsal PAG) and spontaneous defensive behaviors to a predator, the excitatory amino acid D,L-homocysteic acid (5 nmol in 0.1 mu l), was infused into the dorsal PAG and behavioral responses of mice were evaluated in two different situations, a rectangular novel chamber or the Mouse Defense Test Battery (MDTB) apparatus. During a 1-min period following drug infusion, more jumps were made in the chamber than in the MDTB runway but running time and distance traveled were significantly higher in the runway. Animals were subsequently tested using the standard MDTB procedure (anti-predator avoidance, chase and defensive threat/attack). No drug effects on these measures were significant. In a further test in the MDTB apparatus, the pathway of the mouse during peak locomotion response was blocked 3 times by the predator stimulus (anesthetized rat) to determine if the mouse would avoid contact. Ninety percent of D,L-homocysteic treated animals made direct contact with the stimulus (rat), indicating that D,L-homocysteic-induced running is not guided by relevant (here, threat) stimuli. These results indicate that running as opposed to jumping is the primary response in mice injected with D,L-homocysteic into the dorsal PAG when the environment enables flight. However, the lack of responsivity to the predator during peak locomotion suggests that D,L-homocysteic-stimulation into the dorsal PAG does not induce normal antipredator flight. (c) 2006 Published by Elsevier B.V.

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Serotonin (5-HT) can either increase or decrease anxiety-like behaviour in animals, actions that depend upon neuroanatomical site of action and 5-HT receptor subtype. Although systemic studies with 5-HT(2) receptor agonists and antagonists suggest a facilitatory role for this receptor subtype in anxiety, somewhat inconsistent results have been obtained when such compounds have been directly applied to limbic targets such as the hippocampus and amygdala. The present study investigated the effects of the 5-HT(2B/2C) receptor agonist mCPP bilaterally microinjected into the dorsal hippocampus (DH: 0, 0.3 1.0 or 3.0 nmol/0.2 mu l), the ventral hippocampus (VH: 0, 0.3, 1.0 or 3.0 nmol/0.2 mu l) or the amygdaloid complex (0, 0.15, 0.5, 1.0 or 3.0 nmol/0.1 mu l) in mice exposed to the elevated plus-maze (EPM). Test sessions were videotaped and subsequently scored for conventional indices of anxiety (percentage of open arm entries and percentage of open arm time) and locomotor activity (closed arm entries). Results showed that mCPP microinfusions into the DH or VH failed to affect any behavioural measure in the EPM. However, when injected into the amygdaloid complex, the dose of 1.0 nmol of this 5HT(2B/2C) receptor agonist increased behavioural indices of anxiety without significantly altering general activity levels. This anxiogenic-like effect of mCPP was selectively and completely blocked by local injection of a behaviourally-inactive dose of SDZ SER-082 (10 nmol/0.1 mu l), a preferential 5-HT(2C) receptor antagonist. These data suggest that 5HT(2C) receptors located within the amygdaloid complex (but not the dorsal or ventral hippocampus) play a facilitatory role in plus-maze anxiety in mice. (c) 2007 Elsevier B.V. All rights reserved.

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Studies in several laboratories have confirmed the anxiolytic potential of a wide range of 5-HT1A receptor antagonists in rats and mice, with recent evidence pointing to a postsynaptic site of action in the ventral hippocampus. It would, therefore, be predicted that blockade of 5-HT1A somatodendritic autoreceptors in the midbrain raphe nuclei should produce anxiogenic-like effects. To test this hypothesis, we investigated the effects of WAY-100635 microinfusions (0, 1.0 or 3.0 mug in 0.1 mul) into the dorsal (DRN) or median (MRN) raphe nuclei on behaviours displayed by male Swiss-Webster mice in the elevated plus-maze. As this test is sensitive to prior experience. The effects of intra-raphe infusions were examined both in maze-naive and maze-experienced subjects. Sessions, were videotaped and subsequently scored for conventional indices of anxiety (open arm avoidance) and locomotor activity (closed arm entries), as well as a range of ethological measures (e.g. risk assessment). In maze-naive mice, intra-MRN (but not intra-DRN) infusions of WAY-100635 (3.0 mug) increased open arm exploration and reduced risk assessment. Importantly, these effects could not be attributed to a general reduction in locomotor activity. A similar, though somewhat weaker, pattern of behavioural change was observed in maze-experienced animals. This unexpected anxiolytic effect of 5-HT1A autoreceptor blockade in the MRN cannot be accounted fur by a disinhibition of 5-HT release in forebrain targets (e.g. hippocampus and amygdala), where stimulation of postsynaptic 5-HT1A receptors enhances anxiety-like responses. However, as the MRN also projects to the periaqueductal gray matter (PAG), an area known to be sensitive to the anti-aversive effects or 5-HT, it is argued that present results may reflect increased 5-HT release at this crucial midbrain locus within the neural circuitry of defense. (C) 2002 Elsevier B.V. B.V. All rights reserved.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)