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Effect of serotonin transporter genotype on carbon dioxide-induced fear-related behavior in mice
Journal article   Open access   Peer reviewed

Effect of serotonin transporter genotype on carbon dioxide-induced fear-related behavior in mice

Nicole K Leibold, Daniel LA van den Hove, Magdalena T Weidner, Gordon F Buchanan, Harry Wm Steinbusch, Klaus-Peter Lesch and Koen Rj Schruers
Journal of psychopharmacology (Oxford), Vol.34(12), pp.1408-1417
12/2020
DOI: 10.1177/0269881120959611
PMCID: PMC7708670
PMID: 33103571
url
https://doi.org/10.1177/0269881120959611View
Published (Version of record) Open Access

Abstract

Inhaling 35% carbon dioxide induces an emotional and symptomatic state in humans closely resembling naturally occurring panic attacks, the core symptom of panic disorder. Previous research has suggested a role of the serotonin system in the individual sensitivity to carbon dioxide. In line with this, we previously showed that a variant in the gene, encoding the serotonin transporter, moderates the fear response to carbon dioxide in humans. To study the etiological basis of carbon dioxide-reactivity and panic attacks in more detail, we recently established a translational mouse model. The purpose of this study was to investigate whether decreased expression of the serotonin transporter affects the sensitivity to carbon dioxide. Based on our previous work, wildtype and serotonin transporter deficient (+/-, -/-) mice were monitored while being exposed to carbon dioxide-enriched air. In wildtype and serotonin transporter +/- mice, also cardio-respiration was assessed. For most behavioral measures under air exposure, wildtype and serotonin transporter +/- mice did not differ, while serotonin transporter -/- mice showed more fear-related behavior. Carbon dioxide exposure evoked a marked increase in fear-related behaviors, independent of genotype, with the exception of time serotonin transporter -/- mice spent in the center zone of the modified open field test and freezing in the two-chamber test. On the physiological level, when inhaling carbon dioxide, the respiratory system was strongly activated and heart rate decreased independent of genotype. Carbon dioxide is a robust fear-inducing stimulus. It evokes inhibitory behavioral responses such as decreased exploration and is associated with a clear respiratory profile independent of serotonin transporter genotype.
carbon dioxide Panic attacks serotonin transporter panic disorder

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