title: Evidence of a suffocation alarm system sensitive to clinically-effective treatments with the panicolytics clonazepam and fluoxetine.
abstract: Dyspnea, 'hunger for air', and the urge to flee are the cardinal symptoms of respiratory-type panic attacks. Patients also show baseline respiratory abnormalities and a higher rate of comorbid and antecedent respiratory diseases. Panic attacks are also precipitated by both the infusion of 0.5 M sodium lactate and the inhalation of 5-7% carbon dioxide (CO2) in predisposed patients, but not in healthy volunteers nor patients without panic disorder. Further studies show that patients with panic are also hyper-responsive to hypoxia. These and other observations led Klein (1993) to suggest that clinical panic is the misfiring of a suffocation alarm system. In rats, cytotoxic hypoxia of chemoreceptor cells by intravenous injection of potassium cyanide (KCN) produces short-lasting flight behaviors reminiscent of panic attacks. KCN-induced flight behaviors are blocked both by denervation of chemoreceptor cells and lesion of dorsal periaqueductal gray matter, a likely substrate of panic. Herein, we show that KCN-evoked flight behaviors are also attenuated by both acute and chronic treatment with clonazepam (0.01-0.3 mg/kg, intraperitoneally (i.p.)) and fluoxetine (1-4 mg/kg/day, i.p. for 21 days), respectively. Attenuation of KCN-evoked panic-like behaviors by clinically-effective treatment with panicolytics adds fresh evidence to the false suffocation alarm theory of panic disorder.
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo (UFES), Vitória, Brazil.
authors.forename: Fagna Giacomin
authors.initials: FG
authors.lastname: Schimitel
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo (UFES), Vitória, Brazil.
authors.forename: Cláudia Janaina Torres
authors.initials: CJ
authors.lastname: Müller
authors.affiliation: Department of Psychobiology, Federal University of São Paulo (UFSP), São Paulo, Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Tufik
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo (UFES), Vitória, Brazil luiz.schenberg@gmail.com.
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Schenberg
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications / Q000188:drug therapy*; D002998:Clonazepam / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D016584:Panic Disorder / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D011190:Potassium Cyanide; D051381:Rats
chemical_list: D005473:Fluoxetine; D002998:Clonazepam; D011190:Potassium Cyanide
keywords: Alarm system; animal study; clonazepam; dyspnea; fluoxetine; hypoxia; mouse models; panic attack; panic disorder; potassium cyanide; suffocation