The study of the role of serotonin in anxiety has led to the view that this neurotransmitter enhances anxiety, but inhibits panic. Validation of this hypothesis has been made using two experimental procedures that increase anxiety in human volunteers. One is classical conditioning of the skin electrical conductance response, which is assumed to represent anxiety. The other is simulated public speaking, which is believed to mobilize the same neural networks that are operative in panic and social anxiety disorders. In general, the results of these studies have fulfilled the predictions derived from the above hypothesis. The same procedures have been applied to panic disorder patients, and the obtained results have shown that these patients had a blunted anxiety response to public speaking. This speaking stress also did not activate the hypothalamic-pituitary-adrenal axis, which, in contrast, was activated by anticipatory anxiety. It may be concluded that anxiety and panic are qualitatively different emotional states, respectively related to the animal defense reactions to potential and proximal threat. In agreement, reported results of recent neuroimaging studies have shown that anxiety activates prefrontal cortical areas, whereas panic activates midbrain regions, particularly the periaqueductal gray matter. As a general conclusion, it may be said that anxiety, fear and panic do not belong to the same continuum of increasing intensity; instead, they are qualitatively different emotional states.

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.

CONTEXTO: A ansiedade experimental no ser humano constitui-se em ponte entre os modelos animais e os ensaios clínicos. OBJETIVO: Este artigo focaliza métodos químicos e psicológicos utilizados para provocar ansiedade experimental em seres humanos. MÉTODOS: Realizou-se revisão seletiva da literatura. RESULTADOS: Os desafios farmacológicos têm sido usados principalmente para induzir ataques de pânico em pacientes com transtorno de pânico, os quais são mais sensíveis a eles que indivíduos normais ou pacientes portadores de outros transtornos psiquiátricos. Uma das mais importantes contribuições deste método é a de ter mostrado que os agentes panicogênicos mais seletivos, como o lactato ou a inalação de CO2, não ativam o eixo hormonal do estresse. Entre os métodos psicológicos, destacam-se o condicionamento de respostas elétricas da condutância da pele, cujo perfil farmacológico se aproxima daquele do transtorno de ansiedade generalizada, e o teste da simulação do falar em público, cuja farmacologia é semelhante à do transtorno de pânico. CONCLUSÕES: Tais resultados salientam a diferença entre a neurobiologia da ansiedade e a do pânico.

BACKGROUND: Human experimental anxiety methods bridge the gap between animal models and clinical assays. OBJECTIVE: This article is focused on chemical and psychological procedures used to generate experimental anxiety in human beings. METHODS: A selective review of the literature has been carried out. RESULTS: Pharmacological challenges have been mainly used to induce panic attacks in panic disorder patients, who are more susceptible than normal individuals or patients with other psychiatric disorders. One of the most important contributions of this method is to have shown that the most selective panicogenic agents, such as lactate or CO2 inhalation, do not activate the hormonal stress axis. Among the psychological methods stand the conditioning of the electrical skin conductance response, which has a pharmacological profile similar to that of generalized anxiety disorder, and the simulated public speaking test, which is pharmacologically similar to panic disorder. CONCLUSIONS: These results highlight the difference between the neurobiology of anxiety and that of panic.