Evidence of a suffocation alarm system within the periaqueductal gray matter of the rat

Abstract Dyspnea, hunger for air, and urge to flee are the cardinal symptoms of panic attacks. Patients also show baseline respiratory abnormalities and a higher rate of comorbid and antecedent respiratory diseases. Panic attacks are also precipitated by infusion of sodium lactate and inhalation of...

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Published in:	Neuroscience Vol. 200; pp. 59 - 73
Main Authors:	Schimitel, F.G, de Almeida, G.M, Pitol, D.N, Armini, R.S, Tufik, S, Schenberg, L.C
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 03-01-2012 Elsevier
Subjects:	Analysis of Variance Animals Anoxia Anxiety Arousal Asphyxia Asphyxia - pathology Behavior, Animal Biological and medical sciences Carbon dioxide Carbon Dioxide - adverse effects Chemoreceptors (internal) Cyanates - pharmacology cyanide Defecation Defensive behavior defensive behaviors Disease Models, Animal Dose-Response Relationship, Drug Dyspnea Electric Stimulation Escape Reaction - drug effects Escape Reaction - physiology Freezing Reaction, Cataleptic - drug effects Freezing Reaction, Cataleptic - physiology Fundamental and applied biological sciences. Psychology Grooming Hunger Hypercapnia hypoxia Inhalation Jumping Logistic Models Male Medical sciences Nervous system Neurology panic disorder periaqueductal gray Periaqueductal Gray - drug effects Periaqueductal Gray - pathology Periaqueductal Gray - physiopathology Periaqueductal gray area Pneumology potassium cyanide Rats Rats, Wistar Respiratory system : syndromes and miscellaneous diseases Sodium lactate Urination Vertebrates: nervous system and sense organs nucleus retroambiguus medial periaqueductal gray matter hypercapnia median effective intensity LPAG GLP locus coeruleus DR PBA DLPAG dorsal periaqueductal gray DPAG central amygdala TRT χ 2 pontine micturition center (or M-region) premammillary dorsal nucleus Barrington's nucleus CUN hypoxia lateral periaqueductal gray MIC nucleus of the solitary tract cyanide IMO MPAG DMPAG RA dorsal raphe nucleus panic disorder dorsomedial hypothalamus trotting jumping pedunculopontine tegmental nucleus defecation posterior hypothalamus dorsomedial periaqueductal gray NTS galloping chi-square PPT ED 50 ventrolateral periaqueductal gray exophthalmus cuneiform nucleus DMH potassium cyanide VLPAG defensive behaviors DEF immobility PMD parabrachial area PMC dorsolateral periaqueductal gray JMP micturition median effective dose Bar I 50 KCN LC PAG PH periaqueductal gray matter positron emission tomography EXO periaqueductal gray CeA PET Oxygen Rat Respiratory disease Defensive behavior Rodentia Central nervous system Carbon dioxide Environmental factor Encephalon Hypercapnia Vertebrata Mammalia Periaqueductal gray matter Animal Hypoxia
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Summary:	Abstract Dyspnea, hunger for air, and urge to flee are the cardinal symptoms of panic attacks. Patients also show baseline respiratory abnormalities and a higher rate of comorbid and antecedent respiratory diseases. Panic attacks are also precipitated by infusion of sodium lactate and inhalation of 5% CO2 in predisposed patients but not in healthy volunteers or patients without panic disorder. Accordingly, Klein [ Klein (1993) Arch Gen Psychiatry 50:306–317] suggested that clinical panic is the misfiring of an as-yet-unidentified suffocation alarm system. In rats, selective anoxia of chemoreceptor cells by potassium cyanide (KCN) and electrical and chemical stimulations of periaqueductal gray matter (PAG) produce defensive behaviors, which resemble panic attacks. Thus, here we examined the effects of single or combined administrations of CO2 (8% and 13%) and KCN (10–80 μg, i.v.) on spontaneous and PAG-evoked behaviors of rats either intact or bearing electrolytic lesions of PAG. Exposure to CO2 alone reduced grooming while increased exophthalmus, suggesting an arousal response to non-visual cues of environment. Unexpectedly, however, CO2 attenuated PAG-evoked immobility, trotting, and galloping while facilitated defecation and micturition. Conversely, KCN produced all defensive behaviors of the rat and facilitated PAG-evoked trotting, galloping, and defecation. There were also facilitatory trends in PAG-evoked exophthalmus, immobility, and jumping. Moreover, whereas the KCN-evoked defensive behaviors were attenuated or even suppressed by discrete lesions of PAG, they were markedly facilitated by CO2 . Authors suggest that the PAG harbors an anoxia-sensitive suffocation alarm system which activation precipitates panic attacks and potentiates the subject responses to hypercapnia.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2011.10.032