Both alpha(1)- and beta(1)-adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

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

Bed nucleus of the stria terminalis alpha(1) and alpha(2) adrenoceptors differentially modulate the cardiovascular responses to exercise in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Hypothalamic supraoptic but not paraventricular nucleus is involved in cardiovascular responses to carbachol microinjected into the bed nucleus of stria terminalis of unanesthetized rats

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

Bed nucleus of the stria terminalis and the cardiovascular responses to chemoreflex activation

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

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.

Cannabidiol administration into the bed nucleus of the stria terminalis alters cardiovascular responses induced by acute restraint stress through 5-HT1A receptor

Systemic administration of cannabidiol (CBD) is able to attenuate cardiovascular responses to acute restraint stress through activation of 5-HT1A receptors. Previous results from our group suggest that the bed nucleus of the stria terminalis (BNST) is involved in the antiaversive effects of the CBD. Moreover, it has been proposed that synapses within the BNST influence restraint-evoked cardiovascular changes, in particular by an inhibitory influence on the tachycardiac response associated to restraint stress. Thus, the present work investigated the effects of CBD injected into the BNST on cardiovascular changes induced by acute restraint stress and if these effects would involve the local activation of 5-HT1A receptors. The exposition to restraint stress increased both blood pressure and heart rate (HR). The microinjection of CBD (30 and 60nmol) into the BNST enhanced the restraint-evoked HR increase, in a dose-dependent manner, without affecting the pressor response. The selective 5-HT1A receptor antagonist WAY100635 by itself did not change the cardiovascular responses to restraint stress, but blocked the effects of CBD. These results showed that CBD microinjected into the BNST enhanced the HR increase associated with acute restraint stress without affecting the blood pressure response. Although these results are not in agreement with those observed after systemic administration of CBD, they are similar to effects observed after reversible inactivation of the BNST. Moreover, similar to the effects observed after systemic administration, CBD effects in the BNST seem to depend on activation of 5-HT1A receptors. © 2012 Elsevier B.V. and ECNP.

Role of the bed nucleus of the stria terminalis in cardiovascular changes following chronic treatment with cocaine and testosterone: A role beyond drug seeking in addiction?

Neural plasticity has been observed in the bed nucleus of the stria terminalis (BNST) following exposure to both cocaine and androgenic-anabolic steroids. Here we investigated the involvement of the BNST on changes in cardiovascular function and baroreflex activity following either single or combined administration of cocaine and testosterone for 10 consecutive days in rats. Single administration of testosterone increased values of arterial pressure, evoked rest bradycardia and reduced baroreflex-mediated bradycardia. These effects of testosterone were not affected by BNST inactivation caused by local bilateral microinjections of the nonselective synaptic blocker CoCl2. The single administration of cocaine as well as the combined treatment with testosterone and cocaine increased both bradycardiac and tachycardiac responses of the baroreflex. Cocaine-evoked baroreflex changes were totally reversed after BNST inactivation. However, BNST inhibition in animals subjected to combined treatment with cocaine and testosterone reversed only the increase in reflex tachycardia, whereas facilitation of reflex bradycardia was not affected by local BNST treatment with CoCl2. In conclusion, the present study provides the first direct evidence that the BNST play a role in cardiovascular changes associated with drug abuse. Our findings suggest that alterations in cardiovascular function following subchronic exposure to cocaine are mediated by neural plasticity in the BNST. The single treatment with cocaine and the combined administration of testosterone and cocaine had similar effects on baroreflex activity, however the association with testosterone inhibited cocaine-induced changes in the BNST control of reflex bradycardia. Testosterone-induced cardiovascular changes seem to be independent of the BNST. © 2013 IBRO.

CRF1 and CRF2 receptors in the bed nucleus of the stria terminalis modulate the cardiovascular responses to acute restraint stress in rats

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

Involvement of N-methyl-d-aspartate glutamate receptor and nitric oxide in cardiovascular responses to dynamic exercise in rats

Dynamic exercise evokes sustained cardiovascular responses, which are characterized by arterial pressure and heart rate increases. Although it is well accepted that there is central nervous system mediation of cardiovascular adjustments during exercise, information on the role of neural pathways and signaling mechanisms is limited. It has been reported that glutamate, by acting on NMDA receptors, evokes the release of nitric oxide through activation of neuronal nitric oxide synthase (nNOS) in the brain. In the present study, we tested the hypothesis that NMDA receptors and nNOS are involved in cardiovascular responses evoked by an acute bout of exercise on a rodent treadmill. Moreover, we investigated possible central sites mediating control of responses to exercise through the NMDA receptor-nitric oxide pathway. Intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK-801) reduced both the arterial pressure and heart rate increase evoked by dynamic exercise. Intraperitoneal treatment with the preferential nNOS inhibitor 7-nitroindazole reduced exercise-evoked tachycardiac response without affecting the pressor response. Moreover, treadmill running increased NO formation in the medial prefrontal cortex (MPFC), bed nucleus of the stria teminalis (BNST) and periaqueductal gray (PAG), and this effect was inhibited by systemic pretreatment with MK-801. Our findings demonstrate that NMDA receptors and nNOS mediate the tachycardiac response to dynamic exercise, possibly through an NMDA receptor-NO signaling mechanism. However, NMDA receptors, but not nNOS, mediate the exercise-evoked pressor response. The present results also provide evidence that MPFC, BNST and PAG may modulate physiological adjustments during dynamic exercise through NMDA receptor-NO signaling. © 2013 Elsevier B.V.

Efeitos ansiogênicos do óxido nítrico no núcleo intersticial da estria terminal de camundongos

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

Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)