Identifying key modulators of panic attacks in panic disorder: A translational model
AbstractPanic disorder (PD) has a prevalence of 4% in the general population, but its pathophysiology remains elusive. This research focuses on identifying molecular and genetic modulators of unpredictable, recurrent panic attacks which characterize PD. Prior studies revealed that the serotonin transporter, 5-HTT, is involved in fear behavior and that genetic variations might affect panic-related behavior. In order to test these genetic variations on a molecular level a translational model consisting of humans and rodents was used. As follow-up of a human study, 40 male mice (background C57BL/6), wild-type and heterozygous 5-HTT knock-out, were exposed to either 9% CO2 or room air to experimentally provoke fearrelated behavior. Furthermore, the acid-sensing ion channel ASIC1a is hypothesized to be a linking factor between fear detection and fear response. It was tested whether this ASIC1a is expressed in serotonergic neurons in the dorsal raphe nucleus, main source of serotonin, the pivotal neurotransmitter in panic responses. Localization of the ASIC1a channel was determined by use of immunofluorescence. Analysis of the behavioral tests showed no significant difference between genotypes in both air and carbon dioxide condition. Carbon dioxide exposure however increased freezing time in both genotypes. ASIC1a has been indicated in the dorsal raphe and hippocampus in perfusion-fixated rat tissue, but could not yet be detected in the dorsal raphe of the fresh-frozen tissue of tested mice.
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