title: 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.
abstract: 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 hypoxia-sensitive 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 (>60µg) 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-µg 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 CO2alone was ineffective, it potentiated the KCN-evoked 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.
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Cláudia Janaina Torres
authors.initials: CJ
authors.lastname: Müller
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Jeyce Willig
authors.initials: JW
authors.lastname: Quintino-Dos-Santos
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Fagna Giacomin
authors.initials: FG
authors.lastname: Schimitel
authors.affiliation: Department of Psychobiology, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Tufik
authors.affiliation: Department of Pharmaceutic Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Beijamini
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Newton Sabino
authors.initials: NS
authors.lastname: Canteras
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil. Electronic address: luiz.schenberg@gmail.com.
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Schenberg
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004924:Escape Reaction / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010200:Panic / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D011190:Potassium Cyanide / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D011190:Potassium Cyanide
keywords: asphyxia; c-Fos; laterodorsal tegmental nucleus; nucleus of the solitary tract; panic; periaqueductal gray matter