Ansiedade experimental humana

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.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

The hypothalamic-pituitary-adrenal axis in anxiety and panic

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.CNPqFMRPUSP - FAEPA - Hospital das Clínica

Panic Disorder: Is the PAG Involved?

Data from studies with humans have suggested that abnormalities of midbrain structures, including the periaqueductal gray matter (PAG), could be involved in the neurobiology of panic disorder (PD). The electrical stimulation of the PAG in neurosurgical patients induces panic-like symptoms and the effect of drugs that are effective in the treatment of PD in the simulation of public speaking model of anxiety is in agreement with data from animal models of PD. Structural neuroimaging studies have shown increases in gray matter volume of midbrain and pons of PD patients. There is also evidence of lower serotonin transporter and receptor binding, and increases of metabolism in the midbrain of PD patients. Nevertheless, these midbrain abnormalities can not be considered as specific findings, since neuroimaging data indicate that PD patients have abnormalities in other brain structures that process fear and anxiety

Modulation of Emotional Faces Processing and Its Implication for Depression and Anxiety

Non

Anxiolytic-like effect of oxytocin in the simulated public speaking test

Oxytocin (OT) is known to be involved in anxiety, as well as cardiovascular and hormonal regulation. The objective of this study was to assess the acute effect of intranasally administered OT on subjective states, as well as cardiovascular and endocrine parameters, in healthy volunteers (n = 14) performing a simulated public speaking test. OT or placebo was administered intranasally 50 min before the test. Assessments were made across time during the experimental session: (1) baseline (-30 min); (2) pre-test (-15 min); (3) anticipation of the speech (50 min); (4) during the speech (1:03 h), post-test time 1 (1:26 h), and post-test time 2 (1:46 h). Subjective states were evaluated by self-assessment scales. Cortisol serum and plasma adrenocorticotropic hormone (ACTH) were measured. Additionally, heart rate, blood pressure, skin conductance, and the number of spontaneous fluctuations in skin conductance were measured. Compared with placebo, OT reduced the Visual Analogue Mood Scale (VAMS) anxiety index during the pre-test phase only, while increasing sedation at the pre-test, anticipation, and speech phases. OT also lowered the skin conductance level at the pre-test, anticipation, speech, and post-test 2 phases. Other parameters evaluated were not significantly affected by OT. The present results show that OT reduces anticipatory anxiety, but does not affect public speaking fear, suggesting that this hormone has anxiolytic properties.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2002/13197-2]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilFundacao de Apoio ao Ensino, Pesquisa e Assistencia (FAEPA) do Hospital das Clinicas da FMRPUSPCAPE

Evolution of behavioral neuroscience during the last 50 years. Focus on the defense system and neurotransmission.

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.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

lanec-unifesspa/5HT-aggression: Datapackage: Effects of fluoxetine on mirror-induced aggression in two zebrafish phenotypes

Final version of the datapackage (data + analysis scripts + preprint) after preprint submission on bioRxiv

Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze

The beta-adrenergic blocker and 5-HT(1A) receptor antagonist pindolol has been combined with selective serotonin reuptake inhibitors (SSRIs) in patients with depressive and anxiety disorders to shorten the onset of the clinical action and/or increase the proportion of responders. The results of a previous study have shown that pindolol potentiates the panicolytic effect of paroxetine in rats submitted to the elevated T-maze (ETM). Since reported evidence has implicated the 5-HT(1A) receptors of the dorsal periaqueductal gray matter (DPAG) in the panicolytic effect of antidepressants, rats treated with pindolol (5.0 mg/kg, i.p.) and paroxetine (1.5 mg/kg, i.p.) received a previous intra-DPAG injection of the selective 5-HT(1A) antagonist, WAY-100635 (0.4 mu g) and were submitted to the ETM. Pretreatment with WAY-100635 reversed the increase in escape latency, a panicolytic effect, determined by the pindolol-paroxetine combination. These results implicate the 5-HT(1A) receptors of the DPAG in the panicolytic effect of the pindolol-paroxetine combination administered systemically. They also give further preclinical support for the use of this drug combination in the treatment of panic disorder. (C) 2011 Elsevier Ireland Ltd. All rights reserved.CNPq, BrazilCNPqFAEP

Nondiscriminated avoidance of shock by pigeons pecking a key

Four pigeons were trained to avoid shock by pecking a key on a free-operant avoidance schedule in which no exteroceptive stimulus signalled impending shock. Response rate was an inverse function of response-shock interval when shock-shock interval was held constant at 2 sec and response-shock intervals varied from 5 to 40 sec. Amphetamine increased response rates in two subjects and reserpine markedly reduced responding in one