Navegando por Palavras-chave "Elevated T-maze"
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- ItemSomente Metadadados5-HT2A receptor activation in the dorsolateral septum facilitates inhibitory avoidance in the elevated T-maze(Elsevier B.V., 2012-01-01) Paula, Danubia Cristina de [UNIFESP]; Torricelli, Aline Serra [UNIFESP]; Lopreato, Marina Roquette [UNIFESP]; Nascimento, Juliana Olivetti Guzman [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Serotonin in the lateral septum has been implicated in the modulation of defense and hence in anxiety. However, it deserves investigation how changes in 5-HT-mechanisms in this area modulate defensive responses associated with specific subtypes of anxiety disorders. We evaluated the effects of intra-dorsolateral septum (DLS) injections of the preferential 5-HT2A receptor agonist DOI (8 and 16 nmol), the 5-HT2C selective agonist MK-212 (0.1 and 1 nmol) and the preferential 5-HT2A antagonist ketanserin (10 and 20 nmol) in rats exposed to the elevated T-maze (ETM), a model which allows the measurement of two defensive responses: inhibitory avoidance and escape. These responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open-field after the ETM for locomotor activity assessments. Results showed that intra-DLS DOI increased avoidance latencies, an anxiogenic effect. MK and ketanserin were without effect. Also, none of the drugs administered affected the escape performance. Ketanserin blocked the anxiogenic effect caused by DOL. No changes to locomotion were observed. the data suggests that DLS 5-HT2A receptors are involved in the control of inhibitory avoidance and that a failure in this mechanism may be of importance to the physiopathology of generalized anxiety. (C) 2011 Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze(Associação Brasileira de Divulgação Científica, 2012-03-01) Hatano, Viviane Yumi [UNIFESP]; Torricelli, Aline Serra [UNIFESP]; Giassi, Ana Catarina Casari; Coslope, L.a.; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); University of Ottawa Cellular and Molecular Medicine; Parque Nacional da Chapada DiamantinaLippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant’s anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.
- ItemSomente MetadadadosThe blockage of ventromedial hypothalamus CRF type 2 receptors impairs escape responses in the elevated T-maze(Elsevier Science Bv, 2017) Silva, Mariana Santos Carvalho de Faria [UNIFESP]; Souza, Thaissa Marcondes de Oliveira [UNIFESP]; Pereira, Bruno Aranha [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Bittencourt, Jackson C.; Viana, Milena de Barros [UNIFESP]In a previous study, the administration of corticotrophin-releasing factor (CRF) into the dorsomedial hypothalamus (DMH), a region that modulates defensive reactions, was shown to facilitate elevated T-maze (ETM) avoidance responses, an anxiogenic-like effect. Intra-DMH administration of the CRF type 1 receptor (CRFR1) antagonist antalarmin induced anxiolytic-like effects and counteracted the anxiogenic effects of CRF. The present study further investigates the role played by CRF receptors of the medial hypothalamus in anxiety. For that, male wistar rats were treated with CRFR1 and CRFR2-modulating drugs in the DMH or VMH, another hypothalamic nucleus implicated with defensive and emotional behavior, and tested in the ETM for inhibitory avoidance and escape measurements. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. The results showed that intra-VMH CRF or antalarmin did not alter ETM avoidance or escape performance. Intra-VMH injection of the CRFR2 preferential antagonist antisauvagine-30 or of the selective CRFR2 antagonist astressin 2-B inhibited escape performance, a panicolytic-like effect, without altering avoidance reactions. The CRFR2 agonist urocortin-2 intra-VMH was by itself without effect but blocked the effects of astressin 2-B. None of the drugs administered into the DMH altered ETM measurements. Additionally, none of the compounds altered locomotor activity measurements. These results suggest that VMH CRFR2 modulate a defensive response associated with panic disorder and are of relevance to the better understanding of the neural mechanisms underlying this pathological condition.
- ItemSomente MetadadadosChronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis(Elsevier B.V., 2013-08-01) Andrade, José Simões de [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Abrão, Renata Oliveira [UNIFESP]; Santos, Thays Brenner dos [UNIFESP]; Diniz, Leila [UNIFESP]; Britto, Luiz Roberto Giorgetti de; Spadari-Bratfisch, Regina Celia [UNIFESP]; Ortolani, Daniela [UNIFESP]; Melo-Thomas, Liana [UNIFESP]; Silva, Regina Cláudia Barbosa da [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. in unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. in stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. in stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis. (C) 2013 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosCRF type 1 receptors of the medial amygdala modulate inhibitory avoidance responses in the elevated T-maze(Elsevier B.V., 2014-03-01) Vicentini, Jéssica Elias [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Nascimento, Juliana Olivetti Guzman [UNIFESP]; Bittencourt, Jackson C.; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Corticotropin-releasing factor (CRF) plays a critical role in the mediation of physiological and behavioral responses to stressors. in the present study, we investigated the role played by the CRF system within the medial amygdala (MeA) in the modulation of anxiety and fear-related responses. Male Wistar rats were bilaterally administered into the MeA with CRF (125 and 250 ng/0.2 mu l, experiment 1) or with the CRFR1 antagonist antalarmin (25 ng/0.2 mu l, experiment 2) and 10 min later tested in the elevated T-maze (ETM) for inhibitory avoidance and escape measurements. in clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. To further verify if the anxiogenic effects of CRF were mediated by CRFR1 activation, we also investigated the effects of the combined treatment with CRF (250 ng/0.2 mu l) and antalarmin (25 ng/0.2 mu l) (experiment 3). All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Results showed that CRF, in the two doses administered, facilitated ETM avoidance, an anxiogenic response. Antalarmin significantly decreased avoidance latencies, an anxiolytic effect, and was able to counteract the anxiogenic effects of CRF. None of the compounds administered altered escape responses or locomotor activity measurements. These results suggest that CRF in the MeA exerts anxiogenic effects by activating type 1 receptors, which might be of relevance to the physiopathology of generalized anxiety disorder. (C) 2014 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosDeep brain stimulation of the dorsal raphe inhibits avoidance and escape reactions and activates forebrain regions related to the modulation of anxiety/panic(Elsevier Science Bv, 2017) Wscieklica, Tatiana [UNIFESP]; Silva, Mariana Santos Carvalho de Faria [UNIFESP]; Lemes, Jessica Alves [UNIFESP]; Melo-Thomas, Liana; Céspedes, Isabel Cristina [UNIFESP]; Viana, Milena de Barros [UNIFESP]One of the main neurochemical systems associated with anxiety/panic is the serotonergic system originating from the dorsal raphe nucleus (DR). Previous evidence suggests that the DR is composed of distinct subpopulations of neurons, both morphologically and functionally distinct. It seems that mainly the dorsal region of the DR (DRD) regulates anxiety-related reactions, while lateral wings DR (lwDR) serotonin (5-HT) neurons inhibit panic-related responses. In this study we used the technique of deep brain stimulation (DBS) to investigate the role played by the DRD and lwDR in defense. Male Wistar rats were submitted to high-frequency stimulation (100 mu A,100 Hz) in one of the two DR regions for 1 h and immediately after tested in the avoidance or escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been related to generalized anxiety and panic disorder, respectively. After being submitted to the ETM, animals were placed in an open field for locomotor activity assessment. An additional group of rats was submitted to DBS of the DRD or the lwDR and used for quantification of c-Fos immunoreactive (Fos-ir) neurons in brain regions related to the modulation of defense. Results showed that stimulation of the DRD decreased avoidance latencies, an anxiolytic-like effect. DRD stimulation also led to increases in Fos-ir in the medial amygdala, lateral septum and cingulate cortex. DBS applied to the lwDR increased escape latencies, a panicolytic-like effect. This data highlights the importance of raphe topography and the potential benefit of the DBS technique for the treatment of anxiety-related disorders. (C) 2017 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosDorsomedial hypothalamus CRF type 1 receptors selectively modulate inhibitory avoidance responses in the elevated T-maze(Elsevier B.V., 2014-09-01) Silva, Mariana Santos Carvalho de Faria [UNIFESP]; Pereira, Bruno Aranha [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Nascimento, Juliana Olivetti Guzman [UNIFESP]; Bittencourt, Jackson C.; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Corticotropin-releasing factor (CRF) plays a critical role in the mediation of physiological and behavioral responses to stressors. in the present study, we investigated the role played by the CRF system within the dorsomedial hypothalamus (DMH) in the modulation of anxiety- and panic-related responses. Male Wistar rats were administered into the DMH with CRF (125 and 250 ng/0.2 mu l, experiment 1) or with the CRFR1 antagonist antalarmin (25 ng/0.2 mu l, experiment 2) and 10 min later tested in the elevated T-maze (ETM) for inhibitory avoidance and escape measurements. in clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. To further verify if the anxiogenic effects of CRF were mediated by CRFR1 activation, we also investigated the effects of the combined treatment with CRF (250 ng/0.2 mu l) and antalarmin (25 ng/0.2 mu l) (experiment 3). All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Results showed that 250 ng/0.2 mu l of CRF facilitated ETM avoidance, an anxiogenic response. Antalarmin significantly decreased avoidance latencies, an anxiolytic effect, and was able to counteract the anxiogenic effects of CRF. None of the compounds administered altered escape responses or locomotor activity measurements. These results suggest that CRF in the DMH exerts anxiogenic effects by activating type 1 receptors, which might be of relevance to the physiopathology of generalized anxiety disorder. (C) 2014 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosDorsomedial hypothalamus serotonin 1A receptors mediate a panic-related response in the elevated T-maze(Elsevier B.V., 2014-10-01) Nascimento, Juliana Olivetti Guzman [UNIFESP]; Kikuchi, Leticia Sumiko [UNIFESP]; Bortoli, Valquiria Camin de; Zangrossi, Helio; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Espirito Santo; Universidade de São Paulo (USP)The dorsomedial hypothalamus (DMH) has long been associated with the regulation of escape, a panicrelated defensive response. Previous evidence has shown that the activation of serotonin (5-HT) 1A and 2A receptors impairs escape behavior induced by the electrical stimulation of the same region. in this study we further explore the relationship of the DMH with defense by investigating the effects of 5-HT1A activation on escape behavior generated in male Wistar rats by an ethologically based aversive stimuli, exposure to one of the open arms of the elevated T-maze (ETM). Aside from escape, the ETM also allows the measurement of inhibitory avoidance, a defensive response associated with generalized anxiety disorder. To evaluate locomotor activity, after ETM measurements animals were submitted to an open field. Results showed that intra-DMH administration of the 5-HT1A receptor agonist 8-OH-DPAT inhibited escape expression. Local administration of the 5-HT1A antagonist WAY-100635 by its own was ineffective, but blocked the panicolytic-like effect of 8-OH-DPAT. Chronic (21 days) systemic treatment with imipramine potentiated the anti-escape effect of 8-OH-DPAT. No significant effects of treatment with 8-OH-DPAT or imipramine on avoidance latencies or the number of lines crossed in the open field were found: These results indicate that 5-HT1A receptors within the DMH may play a phasic inhibitory role on ETM escape expression. As previously proposed, facilitation of 5-HT1A-mediated neurotransmission in the DMH may be involved in the mechanism of action of anti-panic compounds. (C) 2014 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Efeitos Comportamentais e Imunoistoquímicos da Deep Brain Stimulation Administrada à Porção Dorsal e às Asas Laterais do Núcleo Dorsal da Rafe(Universidade Federal de São Paulo, 2023-05-15) Lemes, Jessica Alves [UNIFESP]; Viana, Milena de Barros [UNIFESP]; http://lattes.cnpq.br/3053794724319601; http://lattes.cnpq.br/6122331252125818; Universidade Federal de São Paulo (UNIFESP)Um dos principais sistemas neuroquímicos associados à modulação da ansiedade e do pânico é o serotonérgico e cerca de 80% dos neurônios serotonérgicos que se projetam para o prosencéfalo tem sua origem em um núcleo mesencefálico, o núcleo dorsal da rafe (NDR). Evidências clínicas e experimentais sugerem que subpopulações neuronais morfológica e funcionalmente distintas compõem a estrutura. Em um estudo prévio, demonstramos que a Deep Brain Stimulation (DBS, em português Estimulação Cerebral Profunda), quando administrada a duas sub-regiões do NDR, o subnúcleo dorsal (DRD) e as asas laterais (alNDR), diminuiu respostas relacionadas, respectivamente, à ansiedade e ao pânico no modelo do labirinto em T elevado (LTE). O presente estudo investigou possíveis alterações neurobiológicas relacionadas a estes efeitos. Para tanto, ratos Wistar machos foram submetidos à DBS de alta frequência (100 μA, 100 Hz), no DRD ou alNDR por 1h, e então testados nas tarefas de esquiva ou de fuga no LTE. Tendo em vista que inibidores seletivos de recaptação de serotonina (5-HT) são tratamentos farmacológicos de primeira opção para diferentes transtornos de ansiedade, os efeitos da administração crônica de fluoxetina (10 mg/kg, IP, 21 dias) foram investigados em um grupo independente de animais para fins de comparação. Após as medidas realizadas no LTE, os animais foram submetidos a um campo aberto para verificação da sua atividade locomotora. Além disso, foi avaliada a imunorreatividade à proteína c-Fos (Fos-ir) e à enzima limitante para síntese de 5-HT, a triptofano hidroxilase (TrpOH-ir). Resultados mostraram que a DBS administrada ao DRD diminuiu respostas de esquiva no LTE, efeito tipo ansiolítico, sem alterar respostas de fuga ou a atividade locomotora dos animais. Já a fluoxetina IP e a DBS administradas às alNDR diminuiram as respostas de fuga, efeito tipo panicolítico, sem alterarem as respostas de esquiva ou a atividade locomotora dos animais. Enquanto a DBS administrada ao DRD diminuiu a dupla marcação no próprio DRD, a DBS administrada às alNDR aumentou a Fos-ir e a dupla marcação no DRD e nas alNDR. A fluoxetina também aumentou a dupla marcação nas alNDR e no subnúcleo ventral (DRV) do NDR, mas a diminuiu no DRD. Estes resultados sugerem que os efeitos tipo ansiolítico e panicolítico da DBS e da fluoxetina estão relacionados à modulação serotonérgica em diferentes subnúcleos do NDR.
- ItemRestritoEfeitos da cocaína crack sobre o comportamento de ratos no labirinto em T elevado e substratos neurais envolvidos(Universidade Federal de São Paulo, 2020-03-19) Rosário, Barbara dos Anjos [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; http://lattes.cnpq.br/9969803499258672; http://lattes.cnpq.br/3053794724319601; http://lattes.cnpq.br/1749327221652788; Universidade Federal de São Paulo (UNIFESP)A cocaína crack, ou simplesmente crack, foi introduzida no Brasil no final da década de 80, e seu uso tem aumentado drasticamente nos últimos anos para todos os grupos socioeconômicos. Hoje, o Brasil é o segundo maior mercado do mundo para a cocaína crack. Usuários de crack apresentam um pior prognóstico quando comparados com usuários de outras drogas ilícitas porque a droga provoca um quadro de dependência mais grave. A exposição repetida a drogas produz neuroadaptações em regiões encefálicas relacionadas à recompensa que modulam tanto o desenvolvimento do consumo compulsivo de drogas, quanto a recaída para a busca de drogas durante a abstinência. Muitas destas neuroadaptações resultam da indução de fatores de transcrição e subsequente regulação da expressão gênica. A família Fos de fatores de transcrição é de particular interesse, já que os membros desta família mostram padrões de indução diferencial em regiões encefálicas após exposição aguda e crônica à cocaína. A retirada da droga produz aumento nos limiares de recompensa e aumento nas respostas do tipo ansiosas. O presente trabalho investigou os efeitos da exposição, em ratos Wistar machos, à cocaína crack após o tratamento subcrônico por 5 dias e retirada da droga por 3 dias, sobre os padrões de comportamento associados à ansiedade e ao pânico, através do modelo do labirinto em T elevado (LTE). Para mensurar a atividade motora destes animais, eles foram testados em um campo aberto. Além disso, foi avaliada a ativação dos substratos neurais envolvidos com estes comportamentos para cada um dos dois grupos, através da análise de imunoistoquímica à proteína Delta FosB. Os resultados mostraram que nos animais submetidos ao tratamento subcrônico com a droga houve aumento das latências de fuga no modelo do LTE, um efeito panicolítico, que foi acompanhado por uma diminuição da ativação de estruturas relacionadas à modulação de respostas relacionadas ao pânico. Já o período de três dias de retirada da droga não interferiu significativamente com as tarefas comportamentais mensuradas no LTE, embora tenha diminuído a ativação de estruturas críticas para a modulação de respostas relacionadas à ansiedade e ao estresse. Esses resultados contribuem para o melhor entendimento dos efeitos neurobiológicos da cocaína crack.
- ItemAcesso aberto (Open Access)Efeitos do Crack em diferentes doses subcrônicas no Comportamento de Ansiedade e Pânico em ratos Wistar Machos no Labirinto em T Elevado e Substratos Neurais Envolvidos(Universidade Federal de São Paulo, 2021-12-09) Nazaré, Maria de Fátima Santana [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Silva, Regina Cláudia Barbosa da [UNIFESP]; http://lattes.cnpq.br/9969803499258672; http://lattes.cnpq.br/7507421915981968; http://lattes.cnpq.br/3053794724319601; http://lattes.cnpq.br/2491714919201602; Universidade Federal de São Paulo (UNIFESP)O crack foi introduzido no Brasil no final de 1980 ou início de 1990, e seu uso tem aumentado dramaticamente nas últimas décadas para todos os grupos socioeconômicos. Hoje, o Brasil é também o maior mercado do mundo para o crack. O crack é um subtipo da cocaína, preparado através da evaporação da mistura de cocaína e uma base, em geral bicarbonato de sódio. Usuários de crack apresentam um pior prognóstico quando comparados com usuários de outras drogas ilícitas porque a droga provoca um quadro de dependência mais grave. A cocaína altera o sistema dopaminérgico, bloqueando a receptação de dopamina. O uso de crack é associado a comorbidades psiquiátricas como transtornos de humor e ansiedade. A exposição repetida a drogas que causam dependência produz neuroadaptações em regiões encefálicas relacionadas à recompensa que modulam tanto o desenvolvimento do consumo compulsivo de drogas e a persistência do “craving” ou fissura, quanto a recaída para a busca de drogas na abstinência. Muitas destas neuroadaptações resultam da indução de fatores de transcrição e subsequente regulação da expressão gênica, que pode ter efeitos potencialmente duradouros na estrutura e função neuronal. A família Fos de fatores de transcrição é de particular interesse, já que os membros desta família mostram padrões de indução diferencial em regiões encefálicas após exposição aguda e crônica à cocaína. Embora o consumo de crack no Brasil seja alto e sua relação com transtornos ansiosos observada, os estudos sobre o tema são escassos. Por isso, o presente trabalho investigou os efeitos da exposição, de ratos Wistar machos, ao crack, após o tratamento subcrônico (por via IP, doses de 18, 25 e 36 mg/kg), sobre os padrões de comportamento associados à ansiedade e ao pânico, através do modelo do LTE. Para mensurar a atividade motora destes animais, após as tarefas do LTE os animais foram testados em um campo aberto. Além disso, foi avaliada a ativação dos substratos neurais envolvidos com estes comportamentos para cada um dos grupos, através da análise de imunoistoquímica à proteína Delta-FosB. Os resultados mostraram que o tratamento subcrônico com 18 mg/kg de crack, via intraperitoneal, resultou em um aumento das latências de fuga no LTE, um efeito panicolítico. Houve também uma diminuição da imunorreatividade à proteína Delta-FosB em estruturas associadas à modulação de respostas relacionadas ao pânico, como as colunas dorsolateral, ventrolateral e lateral da substância cinzenta periaquedutal (SCP) e a porção dorsal do núcleo dorsal da rafe (DRD). Um resultado oposto foi obtido com o tratamento subcrônico com 25 e 36 mg/kg IP: diminuição das latências de fuga, um efeito panicogênico. Houve também um aumento da imunorreatividade para a proteína Delta-FosB nas colunas dorsolateral, dorsomedial e lateral da SCP. O tratamento IP com 25 mg/kg de crack aumentou também a imunorreatividade à proteína DeltaFosB no DRD. Embora tenha induzido aumento das latências de fuga, a dose mais alta de crack (36 mg/kg IP) acarretou alterações motoras no campo aberto.
- ItemSomente MetadadadosEffects of acute restraint and unpredictable chronic mild stress on brain corticotrophin releasing factor mRNA in the elevated T-maze(Elsevier Science Bv, 2018) Andrade, José Simões de [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Abrão, Renata Oliveira [UNIFESP]; da Silva, Joelcimar M.; Ceneviva, Ricardo; Ribeiro, Daniel Araki [UNIFESP]; Bittencourt, Jackson C.; Viana, Milena de Barros [UNIFESP]Corticotrophin releasing factor (CRF) modulates stress/anxiety-related responses. Previous studies showed that exposure to acute restraint and unpredictable chronic mild stress (UCMS) facilitates elevated T-maze (ETM) avoidance responses, an anxiogenic-like effect. This study verified the role of CRF in the modulation of ETM avoidance and escape reactions, in unstressed rats and in animals exposed to acute restraint or to UCMS, by quantifying CRF mRNA concentrations in stress/anxiety-related brain regions, through semiquantitative in situ hybridization. Results showed that stress exposure altered CRF mRNA in regions related to the modulation of stress/anxiety: the cingulate cortex, the hippocampus, the paraventricular and dorsomedial hypothalamus, the medial and central amygdalas, the dorsal region of the dorsal raphe (dDR) and the ventrolateral periaqueductal gray. A regression analysis showed that the anxiogenic-like effects observed in acute restraint animals were particularly associated to increases in CRF mRNA in the paraventricular hypothalamus, medial and central amygdalas and dDR. On the other hand, anxiogenic-like effects observed after UCMS exposure are associated to increases in CRF mRNA in the medial and central amygdalas, in the BNST and in the ventrolateral periaqueductal grey. This observation suggests important differences in the neurocircuitry that mediates responses to acute and chronic stress exposure. CRF mRNA in regions traditionally related to the modulation of panic reactions (the dorsal periaqueductal grey and the lateral wings of the dorsal raphe) were not observed, what might explain the absence of panicogenic-like effects of stress exposure. These results contribute to a better understanding of the role played by CRF in stress/anxiety-related responses.
- ItemAcesso aberto (Open Access)Effects of chronic corticosterone and imipramine administration on panic and anxiety-related responses(Associação Brasileira de Divulgação Científica, 2011-10-01) Diniz, Leila [UNIFESP]; Reis, Bianca Beraldo dos [UNIFESP]; Castro, Glaucia Monteiro de [UNIFESP]; Medalha, Carla Christina [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.
- ItemAcesso aberto (Open Access)Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and anxiety-related responses in rats(Associação Brasileira de Divulgação Científica, 2010-09-01) Nascimento, Juliana Olivetti Guzman [UNIFESP]; Zangrossi Junior, Helio; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)The medial hypothalamus is part of a neurobiological substrate controlling defensive behavior. It has been shown that a hypothalamic nucleus, the dorsomedial hypothalamus (DMH), is involved in the regulation of escape, a defensive behavior related to panic attacks. The role played by the DMH in the organization of conditioned fear responses, however, is less clear. In the present study, we investigated the effects of reversible inactivation of the DMH with the GABA A agonist muscimol on inhibitory avoidance acquisition and escape expression by male Wistar rats (approximately 280 g in weight) tested in the elevated T-maze (ETM). In the ETM, inhibitory avoidance, a conditioned defensive response, has been associated with generalized anxiety disorder. Results showed that intra-DMH administration of the GABA A receptor agonist muscimol inhibited escape performance, suggesting an antipanic-like effect (P < 0.05), without changing inhibitory avoidance acquisition. Although a higher dose of muscimol (1.0 nmol/0.2 µL; N = 7) also altered locomotor activity in an open field when compared to control animals (0.2 µL saline; N = 13) (P < 0.05), the lower dose (0.5 nmol/0.2 µL; N = 12) of muscimol did not cause any motor impairment. These data corroborate previous evidence suggesting that the DMH is specifically involved in the modulation of escape. Dysfunction of this regulatory mechanism may be relevant in the genesis/maintenance of panic disorder.
- ItemSomente MetadadadosEnvironmental enrichment decreases avoidance responses in the elevated T-maze and delta FosB immunoreactivity in anxiety-related brain regions(Elsevier Science Bv, 2018) Lopes, Danielle Abreu [UNIFESP]; Souza, Thaissa Marcondes de Oliveira [UNIFESP]; Andrade, José Simões de [UNIFESP]; Silva, Mariana Santos Carvalho de Faria [UNIFESP]; Antunes, Hanna Karen Moreira [UNIFESP]; Le Sueur-Maluf, Luciana [UNIFESP]; Céspedes, Isabel Cristina [UNIFESP]; Viana, Milena de Barros [UNIFESP]Environmental enrichment (EE) is an animal management technique, which seems to improve adaptation to the experimental conditions of housing in laboratory animals. Previous studies have pointed to different beneficial effects of the procedure in the treatment of several disorders, including psychiatric conditions such as depression. The anxiolytic effects induced by EE, on the other hand, are not as clear. In fact, it has been proposed that EE acts as a mild stressor agent. To better understand the relationship of EE with anxiety-related responses, the present study exposed rats to one week of EE and subsequently tested these animals in the inhibitory avoidance and escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Additionally, analysis of delta FosB protein immunoreactivity (FosB-ir) was used to map areas activated by EE exposure and plasma corticosterone measurements were performed. The results obtained demonstrate that exposure to EE for one week impaired avoidance responses, an anxiolytic-like effect, without altering escape reactions. Also, in animals submitted to the avoidance task EE exposure decreased FosB-ir in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. Although no behavioral differences were observed in animals submitted to the escape task, EE exposure also decreased FosB-ir in the cingulate cortex, hippocampus (dentate gyms), lateral amygdala, paraventricular, anterior and ventromedial hypothalamus, dorsomedial periaqueductal gray and ventral and dorsal region of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety.
- ItemSomente MetadadadosFacilitation of 5-HT2A/2C-mediated neurotransmission in the ventromedial hypothalamic nucleus decreases anxiety in the elevated T-maze(Elsevier B.V., 2011-01-20) Silva, E. S. da [UNIFESP]; Poltronieri, Selma Conceição; Nascimento, Juliana Olivetti Guzman [UNIFESP]; Zangrossi Junior, Helio; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Ctr Univ Votuporanga UNIFEV; Universidade de São Paulo (USP)Previous evidence has shown that facilitation of GABA/benzodiazepine-mediated neurotransmission in the ventromedial hypothalamus (VMH) inhibits both escape and inhibitory avoidance responses generated in the elevated T-maze test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Aside from GABA/benzodiazepine receptors, the VMH also contains a significant number of serotonin (5-HT) receptors, including 1A, 2A and 2C subtypes. the purpose of the present study was to investigate the effect of the activation of 5-HT1A and 5-HT2A/2C receptors in the VMH on defensive behavioral responses in rats submitted to the ETM. for that, male Wistar rats were treated intra-VMH with the 5-HT1A agonist 8-OH-DPAT, with the 5-HT2A/2C agonist DOI, with the 5-HT2C selective agonist MK-212, or with the 5-HT2A/2C antagonist ketanserin and 10 min after were submitted to the ETM. Results showed that both DOI and MK-212 significantly decreased avoidance measurements, an anxiolytic-like effect, without altering escape. 8-OH-DPAT and ketanserin were without effect, although the last drug attenuated the effects of DOI. None of the drugs altered locomotor activity in an open field. These results suggest that 5-HT2A/2C receptors of the VMH are involved in the regulation of inhibitory avoidance and might be of relevance to the physiopathology of generalized anxiety. (C) 2010 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosGABA/benzodiazepine receptors in the ventromedial hypothalamic nucleus regulate both anxiety and panic-related defensive responses in the elevated T-maze(Elsevier B.V., 2007-09-14) Bueno, Cintia Heloina; Zangrossi Junior, Helio; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)It has been shown that facilitation of GABA-mediated neurotransmission in the medial nucleus of the amygdala and the dorsal periaqueductal gray (dPAG) inhibits the escape, but not the inhibitory avoidance response generated in the elevated T-maze test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Previous evidence indicates that the dorsomedial part of the ventromedial hypothalamus (VMHdm), which is interconnected with these two brain areas, is also part of the neurobiological substrate controlling escape behavior. in the present study, we investigated in male Wistar rats whether the intra-VMHdm injection of GABA-modulating drugs differently affect the two defensive tasks measured in the ETNI. the results showed that the microinjection of the benzodiazepine (BZD) receptor agonist midazolam (10, 20 and 40 nmol), the GABA(A) receptor agonist muscimol (2, 4 and 8 nmol) or the GABA(B) receptor agonist baclofen (2, 4 and 8 nmol) impaired inhibitory avoidance and escape performance, an anxiolytic and panicolytic-like effect, respectively. On the other hand, local administration of the BZD inverse agonist FG 7142 (20, 40 and 80 pmol) facilitated both behaviors, suggesting anxiogenic and panicogenic-like effects. These results were not due to motor alterations, since the drugs did not affect exploratory behavior in an open field. the data suggest that GABA(A)/BZD and GABAB receptors within the VMHdm are involved not only in the control of panic-related, but also of anxiety-related behaviors. (c) 2007 Elsevier Inc. All fights reserved.