The brain acid-base homeostasis and serotonin: A perspective on the use of carbon dioxide as human and rodent experimental model of panic.
Panic attacks (PAs), the core feature of panic disorder, represent a common phenomenon in the general adult population and are associated with a considerable decrease in quality of life and high health care costs. To date, the underlying pathophysiology of PAs is not well understood. A unique feature of PAs is that they represent a rare example of a psychopathological phenomenon that can be reliably modeled in the laboratory in panic disorder patients and healthy volunteers. The most effective techniques to experimentally trigger PAs are those that acutely disturb the acid-base homeostasis in the brain: inhalation of carbon dioxide (CO2), hyperventilation, and lactate infusion. This review particularly focuses on the use of CO2 inhalation in humans and rodents as an experimental model of panic. Besides highlighting the different methodological approaches, the cardio-respiratory and the endocrine responses to CO2 inhalation are summarized. In addition, the relationships between CO2 level, changes in brain pH, the serotonergic system, and adaptive physiological and behavioral responses to CO2 exposure are presented. We aim to present an integrated psychological and neurobiological perspective. Remaining gaps in the literature and future perspectives are discussed.
Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), P.O. Box 616, 6200 MD Maastricht, The Netherlands; Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany. Electronic address: nicole.leibold@maastrichtuniversity.nl.
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Leibold
Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), P.O. Box 616, 6200 MD Maastricht, The Netherlands; Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany. Electronic address: d.vandenhove@maastrichtuniversity.nl.
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van den Hove
Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: gabriel.esquivel@maastrichtuniversity.nl.
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Esquivel
Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: klara.decort@maastrichtuniversity.nl.
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De Cort
Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: lies.goossens@maastrichtuniversity.nl.
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Goossens
Department of Health and Technology, Leuven University College, Herestraat 49, 3000 Leuven, Belgium. Electronic address: eveline.strackx@khleuven.be.
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Strackx
Department of Neurology, Yale University School of Medicine, P.O. Box 208018, 15 York Street, New Haven, CT 06520-8018, USA. Electronic address: gordon.buchanan@yale.edu.
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Buchanan
Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: h.steinbusch@maastrichtuniversity.nl.
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Steinbusch
Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), P.O. Box 616, 6200 MD Maastricht, The Netherlands; Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany. Electronic address: kplesch@mail.uni-wuerzburg.de.
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Lesch
Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; Center for the Psychology of Learning and Experimental Psychopathology, Department of Psychology, University of Leuven, Tiensestraat 102, P.O. Box 3726, 3000 Leuven, Belgium. Electronic address: koen.schruers@maastrichtuniversity.nl.
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Schruers
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016584:Panic Disorder / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism*
D002245:Carbon Dioxide; D012701:Serotonin
Animal models; Brain pH; CO(2); Human models; Panic disorder; Serotonin