The brain acid-base homeostasis and serotonin: A perspective on the use of carbon dioxide as human and rodent experimental model of panic

N K Leibold; D L A van den Hove; G Esquivel; K De Cort; L Goossens; E Strackx; G F Buchanan; H W M Steinbusch; K P Lesch; K R J Schruers

doi:10.1016/j.pneurobio.2015.04.001

The brain acid-base homeostasis and serotonin: A perspective on the use of carbon dioxide as human and rodent experimental model of panic

Prog Neurobiol. 2015 Jun:129:58-78. doi: 10.1016/j.pneurobio.2015.04.001. Epub 2015 Apr 27.

Authors

N K Leibold¹, D L A van den Hove², G Esquivel³, K De Cort⁴, L Goossens⁵, E Strackx⁶, G F Buchanan⁷, H W M Steinbusch⁸, K P Lesch⁹, K R J Schruers¹⁰

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ Department of Health and Technology, Leuven University College, Herestraat 49, 3000 Leuven, Belgium. Electronic address: eveline.strackx@khleuven.be.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ 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.

PMID: 25930682
DOI: 10.1016/j.pneurobio.2015.04.001

Abstract

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.

Keywords: Animal models; Brain pH; CO(2); Human models; Panic disorder; Serotonin.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Brain / physiopathology*
Carbon Dioxide / metabolism*
Homeostasis / physiology*
Humans
Hydrogen-Ion Concentration
Panic Disorder / physiopathology*
Serotonin / metabolism*

Substances

Carbon Dioxide
Serotonin