Homoleptic alkenyls of the early transition metals and related compounds

The first stable homoleptic alkenyls of the early transition metals, MRn, (R = C(Ph)=CMe2; M = Ti, Zr, Hf, n = 4; and M = Cr, n = 3) and the related species (C5H5)2MR2 (M = Ti, Zr) and (C5H5)2Zr(Cl)R have been prepared using appropriate organolithium reagents. Cleavage and insertion reactions are reported for the new compounds.

Patterns of fos activation in rat raphe nuclei during feeding behavior

To analyze the differential recruitment of the raphe nuclei during different phases of feeding behavior, rats were subjected to a food restriction schedule (food for 2 h/day, during 15 days). The animals were submitted to different feeding conditions, constituting the experimental groups: search for food (MFS), food ingestion (MFI), satiety (MFSa) and food restriction control (MFC). A baseline condition (BC) group was included as further control. The MFI and MFC groups, which presented greater autonomic and somatic activation, had more FOS-immunoreactive (FOS-IR) neurons. The MFI group presented more labeled cells in the linear (LRN) and dorsal (DRN) nuclei; the MFC group showed more labeling in the median (MRN), pontine (PRN), magnus (NRM) and obscurus (NRO) nuclei; and the MFSa group had more labeled cells in the pallidus (NRP). The BC exhibited the lowest number of reactive cells. The PRN presented the highest percentage of activation in the raphe while the DRN the lowest. Additional experiments revealed few double-labeled (FOS-IR+ 5-HT-IR) cells within the raphe nuclei in the MFI group, suggesting little serotonergic activation in the raphe during food ingestion. These findings suggest a differential recruitment of raphe nuclei during various phases of feeding behavior. Such findings may reflect changes in behavioral state (e.g., food-induced arousal versus sleep) that lead to greater motor activation, and consequently increased FOS expression. While these data are consistent with the idea that the raphe system acts as gain setter for autonomic and somatic activities, the functional complexity of the raphe is not completely understood. (c) 2008 Elsevier B.V. All rights reserved.

Brincar, atividade humana e ferramenta pedagógica no contexto escolar da região metropolitana de natal

This thesis talks about the use of guided educational tools in play and playful in public schools in the Metropolitan Region of Natal (MRN), contributing to the teaching and students learning of basic education in the contents of portuguese and mathematics. We assume that the play is an activity / human need and therefore implies the proper development of children in physical, psychological, biological, cultural, social and historical aspects. We consider the mediation exercised by the teacher in the classroom, and the affection existing between teacher and student, sine qua non terms, so that the truth and fact of the process of teaching and learning occur. Thus, theoretically collaborated Paulo Freire, with his dialogical vision; Lev S. Vygotsky says that we learn and why we develop; Lev S. Vygotsky that states that we learn and for that we develop ourselves; Pierre Bourdieu and the concept of habitus, as something embedded and therefore procedural, and the cultural capital that needs to be fed and (re)meaning at school; Luiz Pereira, Bernard Lahire, Gilles Brougère and others brought their theoretical contributions. The empirical field of research was composed by the Municipal School Professor Ulysses de Góis, located in the neighborhood of Nova Descoberta in Natal, and the Municipal School José Horacio de Góis, located in the community of Guanduba, in São Gonçalo do Amarante, municipalities of the Metropolitan Region of Natal (MRN). We used as methodology the collaborative-action-research as a possible of effective participation of the research subjects, imputing them a voice and performance in the process, and not considering them just observers. The results indicate the effectiveness of the pedagogical tools in play and playful to the learning of students, but that alone is not able to solve all the problems of the school, other referrals need to be secured, as the planning of the actions to be developed in the school and in the classroom, systematized pedagogical orienttion for faculty, family participation/involvement in the school life of students, among other actions that need to be weighted so that education fulfills its role and promote the emancipation of the subject, because in the freireana liberating perspective, "the reading of the world preced the lecture of the word"

Família, aluno e professor: as forças tipológicas da educação básica na região metropolitana de Natal

This work was developed in the research line: "The habitus of study: builder of a new reality in the basic education of metropolitan area Natal" which is being developed with the support of CAPES by the Centre for Education. Acts, especially the problem of academic performance of students in basic education of the public in the Metropolitan Region of Natal (RMN). Thus, the aim of this paper is to construct a typology of students in the 9th year of basic education, attending the public schools (state or municipal) of MRN, 2009, and assess, according to these profiles, what personal characteristics student and their families: economic, social and cultural capital as well as teaching practices create environments capable of favoring a good educational development as measured by the performance obtained in the assessments in mathematics and English language. The data used were provided through the microdata Brazil Exam 2009 held by INEP. We used the methods Grade of Membership (GoM) for construction of profiles relevance of students according to the characteristics already mentioned. With these profiles was verified, which were effectively generating good performance in school curriculum components evaluated. The findings indicate that students belonging to the profile considered good environment, able to achieve better school performance both in Portuguese as in Mathematics, compared to the extreme profiles and adverse deficit

Serotonergic neurons in the median raphe nucleus regulate inhibitory avoidance but not escape behavior in the rat elevated T-maze test of anxiety

Rationale: A wealth of evidence supports the involvement of the serotonergic neurons of the median raphe nucleus (MRN) in anxiety. However, it is presently unclear whether serotonergic pathways arising from this nucleus play distinguishing regulatory roles in defensive behaviors that have been associated with specific subtypes of anxiety disorders. Objectives: To evaluate the role of the MRN serotonergic neurons in the regulation of two defensive behaviors, inhibitory avoidance and escape, which have been related, respectively, to generalized anxiety and panic disorders. Methods: Male Wistar rats were submitted to the elevated T-maze test of anxiety after intra-MRN administration of drugs that either non-selectively or selectively change the activity of the serotonergic neurons. Results: Intra-MRN injection of FG 7142 (0.04 and 0.08 nmol) and kainic acid (0.03 and 0.06 nmol), drugs that non-selectively stimulate the MRN serotonergic neurons, facilitated inhibitory avoidance acquisition, but impaired escape performance. Microinjection of muscimol (0.11 and 0.22 nmol), a compound that non-selectively inhibits the activity of the MRN serotonergic neurons, impaired inhibitory avoidance and facilitated escape performance. Both kainic acid and muscimol also changed rat locomotion in the open-field test. Intra-MRN injection of 8-OH-DPAT (0.6-15 nmol) and WAY-100635 (0.18-0.74 nmol), respectively an agonist and an antagonist of somatodendritic 5-HT1A receptors located on serotonergic neurons of the MRN, only affected inhibitory avoidance-while the former inhibited the acquisition of this behavior, the latter facilitated it. Conclusion: MRN serotonergic neurons seem to be selectively involved in the regulation of inhibitory avoidance in the elevated T-maze. This result supports the proposal that 5-HT pathways departing from this nucleus play an important role in anxiety processing, with implications for pathologies such as generalized anxiety disorder.

Involvement of median raphe nucleus 5-HT1A receptors in the regulation of generalized anxiety-related defensive behaviours in rats

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

5-HT1A receptors in the dorsal hippocampus mediate the anxiogenic effect induced by the stimulation of 5-HT neurons in the median raphe nucleus

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.

Effect of estradiol benzoate microinjection into the median raphe nucleus on contextual conditioning

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

Anxiolytic-like effect of way-100635 microinfusions into the median (but not dorsal) raphe nucleus in mice exposed to the plus-maze: influence of prior test experience

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.

Blockade of 5-HT2 receptors in the periaqueductal grey matter (PAG) abolishes the anxiolytic-like effect of 5-HT1A receptor antagonism in the median raphe nucleus in mice

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

Efeito do lítio sobre a hiperatividade locomotora induzida pela lesão eletrolítica da região do núcleo mediano da rafe em ratos

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.

Anxiolytic-like effects of median raphe nucleus lesion in the elevated T-maze

The cell bodies of 5-HT containing neurons that innervate the limbic forebrain are mainly found in the dorsal raphe nucleus and in the median raphe nucleus (MRN). To assess the role of the median raphe nucleus in anxiety, rats bearing either electrolytic or 5-HT-selective neurotoxic lesion of the MRN were tested in the elevated T-maze. This apparatus consists of two opposed open arms perpendicular to one enclosed arm. Two tasks are performed in succession by the same rat in one experimental session, namely inhibitory avoidance of the open arm, taken as a measure of conditioned anxiety and one-way escape from the open arm, considered as a measure of unconditioned fear. The test was performed 7 days after the electrolytic lesion (3 mA, 10 s) or 14 days after the neurotoxic lesion (5,7-DHT, 8 mug/1 mul). The results showed that while the electrolytic lesion impaired both inhibitory avoidance and one-way escape, the neurotoxic lesion impaired only inhibitory avoidance. Therefore, serotonergic pathways originating in the MRN seem to participate in the modulation of conditioned anxiety but not unconditioned fear. Other neurotransmitter systems that either originate in or pass through the MRN may regulate unconditioned fear. (C) 2003 Elsevier B.V. All rights reserved.

Role of 5-HT in stress, anxiety, and depression

There are conflicting results on the function of 5-HT in anxiety and depression. To reconcile this evidence, Deakin and Graeff have suggested that the ascending 5-HT pathway that originates in the dorsal raphe nucleus (DRN) and innervates the amygdala and frontal cortex facilitates conditioned fear, while the DRN-periventricular pathway innervating the periventricular and periaqueductal gray matter inhibits inborn fight/flight reactions to impending danger, pain, or asphyxia. To study the role of the DRN 5-HT system in anxiety, we microinjected 8-OH-DPAT into the DRN to inhibit 5 HT release. This treatment impaired inhibitory avoidance (conditioned fear) without affecting one-way escape (unconditioned fear) in the elevated T-maze, a new animal model of anxiety. We also applied three drug treatments that increase 5-HT release from DRN terminals: 1) intra-DRN microinjection of the benzodiazepine inverse agonist FG 4172, 2) intra-DRN microinjection of the excitatory amino acid kainic acid, and 3) intraperitoneal injection of the 5-HT releaser and uptake blocker D-fenfluramine. All treatments enhanced inhibitory avoidance in the T-maze. D-Fenfluramine and intra-DRN kainate also decreased one-way escape. In healthy volunteers, D-fenfluramine and the 5-HT agonist mCPP (mainly 5-HT2C) increased, while the antagonists ritanserin (5-HT2A/(2C)) and SR 46349B (5-HT2A) decreased skin conductance responses to an aversively conditioned stimulus (tone). In addition, D-fenfluramine decreased, whereas ritanserin increased subjective anxiety induced by simulated public speaking, thought to represent unconditioned anxiety. Overall, these results are compatible with the above hypothesis. Deakin and Graeff have suggested that the pathway connecting the median raphe nucleus (MRN) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress. In the present study, we found that 24 h after electrolytic lesion of the rat MRN glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin A was depressed. Seven days after the same lesion, the ulcerogenic effect of restraint was enhanced. Microinjection of 8-OH-DPAT, the nonselective agonist 5-MeO-DMT, or the 5-HT uptake inhibitor zimelidine into the dorsal hippocampus immediately after 2 h of restraint reversed the deficits of open arm exploration in the elevated plus-maze, measured 24 h after restraint. The effect of the two last drugs was antagonized by WAY-100135, a selective 5-HT1A receptor antagonist. These results are compatible with the hypothesis that the MRN-dorsal hippocampus 5-HT system attenuates stress by facilitation of hippocampal 5-HT1A-mediated neurotransmission. Clinical implications of these results are discussed, especially with regard to panic disorder and depression.

Anxiolytic effect of estradiol in the median raphe nucleus mediated by 5-HT1A receptors

Estrogen deficiency has been associated with stress, anxiety and depression. Estrogen receptors have been identified in the median raphe nucleus (MRN). This structure is the main source of serotonergic projections to the hippocampus, a forebrain area implicated in the regulation of defensive responses and in the resistance to chronic stress. There is evidence showing that estrogen modulates 5-HT1A receptor functions. In the MRN, somatodendritic 5-HT1A receptors control the activity of serotonergic neurones by negative feedback. The present study evaluated the effect of intra-MRN injection of estradiol benzoate (EB) (600 or 1200 ng/0.2 mu l) on the performance of ovariectomised rats submitted to the elevated plus-maze test of anxiety and to the open-field test. Additionally, the same effect was evaluated with a previous intra-MRN injection of WAY 100635 (100 ng/0.2 mu l), an antagonist of 5-HT1A receptors. The results showed that both doses of EB increased the percentage of entries and the percentage of time spent into the open arms, suggestive of an anxiolytic effect. The highest dose of the drug also increased the number of entries into the enclosed arm and locomotion in the open field, indicating a stimulatory motor effect. WAY 100635 antagonised the effect of estradiol in the elevated plus-maze and in the open-field. The results show that estrogen receptors of the MRN are implicated in the regulation of anxiety-related behaviour. The results also support claims that the effect of estrogen involves a change in 5-HT1A receptor function. (C) 2005 Elsevier B.V. All rights reserved.

Effect of electrolytic and neurotoxic lesions of the median raphe nucleus on anxiety and stress

To study the role played by 5-HT mechanisms of the MRN, behavioural and physiological parameters were presently measured in rats having either electrolytic or 5,7-dihydroxytryptamine (5,7-DHT) lesion of the MRN made 7 days before testing. Half the animals were submitted to 2-h restraint 24 h before the test. In the elevated plus-maze, the electrolytic lesion increased the percentage of open-arm entries and of time spent on open arms - an anxiolytic effect - in both restrained and nonrestrained rats. The neurotoxic lesion had a similar effect, but only on restrained rats. Restraint had anxiogenic effect. The electrolytic lesion increased transitions between the light and dark compartments and the time spent in the bright compartment of the light-dark box in both restrained and nonrestrained rats. The neurotoxic lesion only increased bright time in restrained rats. The incidence, number and size of gastric ulcers were increased by either the electrolytic or the neurotoxic lesion in both restrained and nonrestrained animals. Both types of lesion depleted 5-HT in the hippocampus in restrained and nonrestrained rats. Restraint increased 5-HT levels. These results implicate 5-HT mechanisms of the median raphe nucleus in the regulation of anxiety and in the genesis of gastric stress ulcers. (C) 2001 Elsevier B.V. All rights reserved.