ABSTRACT
A evolução da Neurociência Comportamental nos últimos 50 anos é apresentada em função das pesquisas desenvolvidas pelo autor e colaboradores na área de Neuropsicofarmacologia. A principal linha de investigação relatada aborda o papel da serotonina na regulação das repostas de defesa, que estão relacionadas com as emoções ansiedade, medo e pânico, bem como com as respectivas patologias: transtorno de ansiedade generalizada, fobias e pânico. As estruturas cerebrais críticas para a ansiedade amígdala, hipocampo e ínsula estão localizadas no cérebro anterior, enquanto que as relacionadas com o medo e o pânico hipotálamo e matéria cinzenta periaquedutal (MCP) situam-se no diencéfalo e no tronco cerebral. Dá-se ênfase ao papel da MCP nas reações a ameaças proximais imobilidade , fuga e luta que estão relacionadas com ataques de pânico. São relatados resultados obtidos em modelos animais de pânico e em experimentação com seres humanos, incluindo testes de ansiedade experimental e neuroimagem morfométrica e funcional, cujas implicações para o conhecimento da fisiopatologia do transtorno de pânico e seu tratamento farmacológico são discutidas. (AU)
The evolution of Behavioral Neuroscience along the last 50 years is presented on the basis of the research work carried out by the author and his coworkers. The main line of investigation reported deals with the role of serotonin in the regulation of defense reactions that are related to the emotions anxiety, fear and panic, as well as to the respective pathologies: generalized anxiety disorder, phobias and panic disorder. The key brain structures for anxiety amygdala, hippocampus and insula are localized in the forebrain, whereas those related to fear and panic hypothalamus and periaqueductal gray matter (PAG) are placed in the diencephalon and brain stem. The role of the defense reactions to proximal danger immobility, flight and fight that are related to panic attacks are highlighted. The results obtained in animal models of anxiety and panic, as well as in humans, including experimental anxiety tests and morphometric and functional neuroimaging are reported, and their implications for the knowledge of the pathophysiology of panic disorder and its pharmacological treatment are discussed. (AU)
Subject(s)
Anxiety , Panic , Magnetic Resonance Imaging , Serotonin , Models, Animal , Human ExperimentationABSTRACT
This review article focuses on the differential activation of the hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety and panic. The results of experimental studies that assayed adrenocorticotropic hormone, cortisol and prolactin show that real-life panic attacks as well as those induced by selective panicogenic agents, such as lactate and carbon dioxide, do not activate the HPA axis. Accordingly, experiments carried out in two animal models of panic, namely electrical stimulation of the dorsal periaqueductal gray matter of the rat and the escape from the open arm of the elevated T maze, have shown that in neither case stress hormones are increased in the plasma. Also in humans, reported results have shown that neither cortisol nor prolactin levels were increased following simulated public speaking, an experimental task that has been related to panic, in either healthy volunteers or patients with panic disorder diagnosis. Therefore, although the panic attack causes a major sympathetic stimulation, it has little effect on the HPA axis. In contrast, anticipatory or generalized anxiety activates both the HPA and the sympatho-adrenal axes.
Subject(s)
Anxiety , Hormones , Panic , Periaqueductal Gray , Stress, PsychologicalABSTRACT
Modelos etofarmacológicos de ansiedade têm sido usados na seleçäo de drogas ansiolíticas. O presente trabalho analisa alguns desses modelos animais, enfatizando a validade de prediçäo para a seleçäo de ansiolíticos benzodiazepínicos (BDZs) e serotonérgicos. De uma maneira geral, esses estudos indicam que drogas serotonérgicas promovem efeitos ansiolíticos menos consistentes do que o BDZs, com alguns modelos mostrando efeitos contraditórios