ON THE VERGE OF A RESPIRATORY-TYPE PANIC ATTACK: SELECTIVE ACTIVATIONS OF ROSTROLATERAL AND CAUDOVENTROLATERAL PERIAQUEDUCTAL GRAY MATTER FOLLOWING SHORT-LASTING ESCAPE TO A LOW DOSE OF POTASSIUM CYANIDE

Intravenous injections of potassium cyanide (KCN) both elicit escape by its own and facilitate escape to electrical stimulation of the periaqueductal gray matter (PAG). Moreover, whereas the KCN-evoked escape is potentiated by CO2, it is suppressed by both lesions of PAG and clinically effective treatments with panicolytics. These and other data suggest that the PAG harbors a hypoxiasensitive alarm system the activation of which could both precipitate panic and render the subject hypersensitive to CO2. Although prior c-Fos immunohistochemistry studies reported widespread activations of PAG following KCN injections, the employment of repeated injections of high doses of KCN (> 60 mu g) in anesthetized rats compromised both the localization of KCN-responsive areas and their correlation with escape behavior. Accordingly, here we compared the brainstem activations of saline-injected controls (air/saline) with those produced by a single intravenous injection of 40-mu g KCN (air/KCN), a 2-min exposure to 13% CO2 (CO2/saline), or a combined stimulus (CO2/KCN). Behavioral effects of KCN microinjections into the PAG were assessed as well. Data showed that whereas the KCN microinjections were ineffective, KCN intravenous injections elicited escape in all tested rats. Moreover, whereas the CO2 alone was ineffective, it potentiated the KCNevoked escape. Compared to controls, the nucleus tractus solitarius was significantly activated in both CO2/saline and CO2/KCN groups. Additionally, whereas the laterodorsal tegmental nucleus was activated by all treatments, the rostrolateral and caudoventrolateral PAG were activated by air/KCN only. Data suggest that the latter structures are key components of a hypoxia-sensitive suffocation alarm which activation may trigger a panic attack. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.CAPESCNPqConselho Nacional de Desenvolvimento Cientifico e Tecnologico/Fundacao de Amparo a Pesquisa do Espirito Santo (CNPq/FAPES)Universidade Federal do Espirito Santo/Associacao Fundo de Incentivo a Pesquisa (UFES/AFIP)Univ Fed Espirito Santo, Dept Physiol Sci, Vitoria, ES, BrazilUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, SP, BrazilUniv Fed Espirito Santo, Dept Pharmaceut Sci, Vitoria, ES, BrazilUniv Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, SP, BrazilCNPq/FAPES: 55203345/11UFES/AFIP: 23068.020409/2010-43Web of Scienc

Translational approach to studying panic disorder in rats: Hits and misses

Luiz Carlos Schenberg, Fagna Giacomin Schimitel, Rubia de Souza Armini, Cristian Setubal Bernabe, Caroline Azevedo Rosa, Sergio Tufik, Claudia Janaina Torres Muller, Jeyce Willig Quintino-dos-Santos. Translational Approach to Studying Panic Disorder in Rats: Hits and Misses. Neurosci. Biobehav. Rev. XX (X) XXX-XXX, 2014. Panic disorder (PD) patients are specifically sensitive to 5-7% carbon dioxide. Another startling feature of clinical panic is the counterintuitive lack of increments in 'stress hormones'. PD is also more frequent in women and highly comorbid with childhood separation anxiety (CSA). On the other hand, increasing evidence suggests that panic is mediated at dorsal periaqueductal grey matter (DPAG). in line with prior studies showing that DPAG-evoked panic-like behaviours are attenuated by clinically-effective treatments with panicolytics, we show here that (i) the DPAG harbors a hypoxia-sensitive alarm system, which is activated by hypoxia and potentiated by hypercapnia, (ii) the DPAG suffocation alarm system is inhibited by clinically-effective treatments with panicolytics, (iii) DPAG stimulations do not increase stress hormones in the absence of physical exertion, (iv) DPAG-evoked panic-like behaviours are facilitated in neonatally-isolated adult rats, a model of CSA, and (v) DPAG-evoked responses are enhanced in the late diestrus of female rats. Data are consistent with the DPAG mediation of both respiratory and non-respiratory types of panic attacks. (C) 2014 Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UFES/AFIPUniv Fed Espirito Santo, Dept Physiol Sci, Vitoria, ES, BrazilUniv Fed Espirito Santo, Dept Sports, Vitoria, ES, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilCNPq: 55203345/11UFES/AFIP: 23068020409/2010-43Web of Scienc