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.

Cognitive Deficits in Machado-Joseph Disease Correlate with Hypoperfusion of Visual System Areas

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

Anxiogenic-like effects induced by NMDA receptor activation are prevented by inhibition of neuronal nitric oxide synthase in the periaqueductal gray in mice

Glutamate-NMDA (N-methyl-D-aspartate) receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction. We have recently demonstrated that the vigorous defensive-like behaviors (e.g. jumping and running) and antinociception induced by intra-PAG injection of N-methyl-D-aspartate (NMDA) were completely blocked by prior infusion of N(omega)-propyl-L-arginine (NPLA), a specific neuronal nitric oxide synthesis (nNOS) enzyme inhibitor, into the same midbrain structure. It remains unclear however, whether the inhibition of nNOS within the mouse PAG changes the anxiety-like behavior per se or the effects of the inhibition of nNOS depend on the suppression of downstream of glutamate-NMDA receptor activation. This study investigated whether intra-PAG infusion of NPLA (i) attenuates anxiety in the elevated plus-maze (EPM) and (ii) antagonizes the anxiogenic-like effects induced by intra-PAG injection of NMDA. 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 intra-PAG infusions of NPLA (0.2, 0.4 or 0.8 nmol/0.1 mu l) did not alter significantly any behavioral response in the EPM when compared to control group (Experiment 1). Intra-PAG infusion of NMDA (0 and 0.02 nmol/0.1 mu l; a dose that does not provoke vigorous defensive behaviors per se in mice) significantly reduced open arm exploration, confirming an anxiogenic-like effect (Experiment 2). When injected into the PAG 10 min prior local NMDA injection (0.02 nmol/0.1 mu l), NPLA (0.4 nmol/0.1 mu l) was able to revert the anxiogenic-like effect of glutamate-NMDA receptor activation. Neither intra-PAG infusion of NMDA nor NPLA altered closed arm entries, a widely used measure of locomotor activity in the EPM. These results suggest that intra-PAG nitric oxide synthesis does not play a role on anxiety-like behavior elicited during EPM exposure; however its synthesis is important for the proaversive effects produced by activation of glutamate-NMDA receptors located within this limbic midbrain structure. (C) 2008 Elsevier B.V. All rights reserved.

The anatomical connections of the macaque monkey orbitofrontal cortex. A review

The orbitofrontal cortex (OfC) is a heterogeneous prefrontal sector selectively connected with a wide constellation of other prefrontal, limbic, sensory and premotor areas. Among the limbic cortical connections, the ones with the bippocampus and parabippocampal cortex are particularly salient. Sensory cortices connected with the OfC include areas involved in olfactory, gustatory, somatosensory, auditory and visual processing. Subcortical structures with prominent OfC connections include the amygdala, numerous thalamic nuclei, the striatum, hypothalamus, periaqueductal gray matter, and biochemically specific cell groups in the basal forebrain and brainstem. Architectonic and connectional evidence supports parcellation of the OfC. The rostrally placed isocortical sector is mainly connected with isocortical areas, including sensory areas of the auditory, somatic and visual modalities, whereas the caudal non-isocortical sector is principally connected with non-isocortical areas, and, in the sensory domain, with olfactory and gustatory areas. The connections of the isocortical and non- isocortical orbital sectors with the amygdala, thalamus, striatum, hypotbalamus and periaqueductal gray matter are also specific. The medial sector of the OfC is selectively connected with the bippocampus, posterior parabippocampal cortex, posterior cingulate and retrosplenial areas, and area prostriata, while the lateral orbitofrontal sector is the most heavily connected with sensory areas of the gustatory, somatic and visual modalities, with premotor regions, and with the amygdala.

Toward an Explanation of the Genesis of Ketamine-Induced Perceptual Distortions and Hallucinatory States

The NMDA receptor (NMDAR) channel has been proposed to function as a coincidence-detection mechanism for afferent and reentrant signals, supporting conscious perception, learning, and memory formation. In this paper we discuss the genesis of distorted perceptual states induced by subanesthetic doses of ketamine, a well-known NMDA antagonist. NMDAR blockage has been suggested to perturb perceptual processing in sensory cortex, and also to decrease GABAergic inhibition in limbic areas (leading to an increase in dopamine excitability). We propose that perceptual distortions and hallucinations induced by ketamine blocking of NMDARs are generated by alternative signaling pathways, which include increase of excitability in frontal areas, and glutamate binding to AMPA in sensory cortex prompting Ca++ entry through voltage-dependent calcium channels (VDCCs). This mechanism supports the thesis that glutamate binding to AMPA and NMDARs at sensory cortex mediates most normal perception, while binding to AMPA and activating VDCCs mediates some types of altered perceptual states. We suggest that Ca++ metabolic activity in neurons at associative and sensory cortices is an important factor in the generation of both kinds of perceptual consciousness.

Mechanisms in the bed nucleus of the stria terminalis involved in control of autonomic and neuroendocrine functions: A review

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

Noradrenergic neurotransmission within the bed nucleus of the stria terminalis modulates the retention of immobility in the rat forced swimming test

The bed nucleus of the stria terminalis (BNST) is a limbic structure that has a direct influence on the autonomic, neuroendocrine, and behavioral responses to stress. It was recently reported that reversible inactivation of synaptic transmission within this structure causes antidepressant-like effects, indicating that activation of the BNST during stressful situations would facilitate the development of behavioral changes related to the neurobiology of depression. Moreover, noradrenergic neurotransmission is abundant in the BNST and has an important role in the regulation of emotional processes related to the stress response. Thus, this study aimed to test the hypothesis that activation of adrenoceptors within the BNST facilitates the development of behavioral consequences of stress. To investigate this hypothesis, male Wistar rats were stressed (forced swimming, 15 min) and 24 h later received intra-BNST injections of vehicle, WB4101, RX821002, CGP20712, or ICI118,551, which are selective α1, α2, β1, and β2 adrenoceptor antagonists, respectively, 10 min before a 5-min forced swimming test. It was observed that administration of WB4101 (10 and 15 nmol), CGP20712 (5 and 10 nmol), or ICI118,551 (5 nmol) into the BNST reduced the immobility time of rats subjected to forced swimming test, indicating an antidepressant-like effect. These findings suggest that activation of α1, β1, and β2 adrenoceptors in the BNST could be involved in the development of the behavioral consequences of stress. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Alterações de fluxos sanguíneos cerebrais regionais (FSCr) avaliados através de SPECT (Single Photon Emission Computed Tomography) em pacientes com câncer de mama submetidas à quimioterapia adjuvante

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Mapeamento de regiões de ativação cerebral durante tarefas deglutórias por imagens de ressonância magnética funcional

INTRODUÇÃO: A deglutição é um processo fisiológico complexo que acontece por uma sequência motora automática, regulada por um complicado mecanismo neuromotor e neuromuscular que é iniciado de maneira consciente e é resultado da integridade anatômica e funcional de diversas estruturas faciais. É de extrema importância para a nutrição do organismo como um todo. Um dos maiores desafios no campo das ciências é identificar os substratos neurais de comportamentos fisiológicos, incluindo esse processo de deglutição. O desenvolvimento da tecnologia em neuroimagem funcional nos últimos anos está provocando um rápido avanço no conhecimento de funções cerebrais, o que resultou numa explosão de novos achados em neurociência. OBJETIVO: Mapear as regiões de ativação cerebral durante o fenômeno da deglutição por meio do exame de ressonância magnética funcional. MÉTODO: Participaram do estudo quatro indivíduos do sexo feminino, com idade entre 18 e 30 anos, sem alterações neurológicas, estruturais e alimentares. Após a aprovação da Instituição (Clínica Lobo), do Comité de Ética e Pesquisa do Instituto de Ciências da Saúde (ICS) e a aprovação escrita de cada paciente através do termo de consentimento livre e esclarecido, foram submetidos a quatro provas deglutórias, utilizando a técnica de ressonância magnética funcional. RESULTADOS: Foi possível a determinação da ativação dos hemisférios cerebrais e cerebelares e as especificas áreas que os compõem. Mesmo com uma amostragem pequena, os resultados das análises individuais mostraram padrões de acordo com a literatura, conjuntamente com dados novos. DISCUSSÃO: O cerebelo é responsável pela coordenação da ação motora e manutenção da harmonia dos movimentos, posição e equilíbrio do bolo alimentar; o bolbo raquidiano juntamente com o tronco cerebral constitui o centro de atividades reflexas que controla funções ou respostas orgânicas automáticas como a deglutição; o mesencéfalo é a parte do encéfalo que coordena a informação visual; o tálamo encaminha quase todo o tipo de informação sensorial para as zonas específicas do córtex cerebral; o hipotálamo, importante na experimentação das sensações de prazer, regula as funções homeostáticas do corpo, gustação, olfação, salivação, interagindo com o sistema nervoso autônomo e o sistema límbico está ligado ao controle e direção das reações emocionais, sob a ação da amígdala, no processamento de odores e no armazenamento de conteúdos da memória, aqui através do hipocampo. CONCLUSÃO: O ato de deglutir é um processo complexo, ativando muitas áreas cerebrais, dentre elas podemos destacar a gustativa, mental/visual e a olfativa e que é iniciado muito antes dos processos mecânicos envolvidos, conforme demonstrado pelas áreas corticais e subcorticais ativadas. A área olfativa foi a mais notadamente destacada nas imagens colhidas pela Rmf.

Efeitos da exposição crônica ao etanol da adolescência à fase adulta em ratos sobre o processo mnemônico e na densidade celular no hipocampo

O sistema nervoso central é vulnerável a ação de inúmeras substâncias, dentre estas se encontram as substâncias psicoativas, tal como o álcool etílico ou etanol, que é consumida pela humanidade há bastante tempo e está associado a uma gama de problemas médico sociais. Sendo assim, o objetivo deste trabalho foi investigar as alterações neurocomportamentais e teciduais decorrentes da exposição ao etanol da adolescência à fase adulta sobre o hipocampo. Para isto, foram avaliadas 30 ratas Wistar, distribuídas em grupo controle e etanol, que ao completarem 35 dias de idade (adolescência) receberam, por gavagem, etanol na dose de 6,5 g/Kg/dia até completar 90 dias (fase adulta). Após esse período, os animais foram submetidos aos ensaios comportamentais do campo aberto, reconhecimento social e a esquiva inibitória e posteriormente perfundidos para avaliação tecidual através de processamento histológico por violeta de cresila. Foram coletadas e processadas secções de 50 μm, as amostras foram submetidas à coloração por violeta de cresila. Os resultados demonstraram déficit nos parâmetros analisados nos ensaios comportamentais, como comprometimento na deambulação natural do animal, no percentual no número de quadrantes centrais e tempo na área central o que sugere comportamento do tipo ansiogênico, aumento no número de levantamentos relacionado à atividade exploratória dos animais. Observou-se comprometimento no desenvolvimento de processos mnemônicos com diminuição na retenção de memória de curto e longo prazo, bem como na de reconhecimento social. Quanto ao tratamento histológico foi observado diminuição na densidade celular nas regiões CA1 e CA3 do hipocampo. Estes resultados indicam que a exposição crônica ao etanol da adolescência a fase adulta perturba aspectos comportamentais relacionados ao sistema límbico, no qual o hipocampo esta inserido.

Both alpha(1)- and alpha(2)-adrenoceptors in the Insular Cortex Are Involved in the Cardiovascular Responses to Acute Restraint Stress in Rats

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

Neurophysiological aspects of musical auditory stimulation on cardiovascular system

Introduction: The literature has shown that musical stimulation can influence the cardiovascular system, however, the neurophysiological aspects of this influence are not yet fully elucidated. Objective: This study describes the influence of music on the neurophysiological mechanisms in the human body, specifically the variable blood pressure, as well as the neural mechanisms of music processing. Methods: Searches were conducted in Medline, PEDro, Lilacs and SciELO using the intersection of the keyword “music” with the keyword descriptors “blood pressure” and “neurophysiology”. Results: There were selected 11 articles, which indicated that music interferes in some aspects of physiological variables. Conclusion: Studies have indicated that music interferes on the control of blood pressure, heart and respiratory rate, through possible involvement of limbic brain areas which modulate hypothalamic-pituitary functions. Further studies are needed in order to identify the mechanisms by which this influence occurs.

Tonic modulation of anxiety-like behavior by corticotropin-releasing factor (CRF) type 1 receptor (CRF1) within the medial prefrontal cortex (mPFC) in male mice: Role of protein kinase A (PKA)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Contrasting effects of nitric oxide and corticotropin-releasing factor within the dorsal periaqueductal gray on defensive behavior and nociception in mice

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

Psychiatric comorbidity in refractory focal epilepsy: A study of 490 patients

We studied the prevalence and associated factors of psychiatric comorbidities in 490 patients with refractory focal epilepsy. Of these, 198 (40.4%) patients had psychiatric comorbidity. An Axis I diagnosis was made in 154 patients (31.4%) and an Axis II diagnosis (personality disorder) in another 44 (8.97%) patients. After logistic regression, positive family history of psychiatric comorbidities (O.R.=1.98; 95% CI=1.10-3.58; p=0.023), the presence of Axis II psychiatric comorbidities (O.R.=3.25; 95% CI=1.70-6.22; p<0.0001), and the epileptogenic zone located in mesial temporal lobe structures (O.R.=1.94; 95% CI=1.25-3.03; p=0.003) remained associated with Axis I psychiatric comorbidities. We concluded that a combination of clinical variables and selected structural abnormalities of the central nervous system contributes to the development of psychiatric comorbidities in patients with focal epilepsy. (C) 2012 Published by Elsevier Inc.