Genetically driven brain serotonin deficiency facilitates panic-like escape behavior in mice

• DOI: 10.1038/tp.2017.209
• Publication Date: 2017-10-03T13:40:45Z
• Authors: J Waider; S Popp; M D Lange; R Kern; J F Kolter; J Kobler; N C Donner; K R Lowe; J H Malzbender; C J Brazell; M R Arnold; B Aboagye; A Schmitt-Böhrer; C A Lowry; H C Pape; K P Lesch
• Keywords: TPH2; Basolateral amygdala; Dorsal raphe nucleus; Agoraphobia; Tryptophan hydroxylase; Raphe nuclei

Abstract Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology stressor-related and anxiety disorders. Here we investigate influence constitutively deficient 5-HT synthesis on anxiety-like behaviors using Tryptophan hydroxylase 2 ( Tph2 ) mutant mice. Functional assessment c-Fos after associated foot shock, electrophysiological recordings GABAergic synaptic transmission, differential expression Slc6a4 gene serotonergic neurons were combined with locomotor measurements different contextual settings. Our findings indicate that constitutive inactivation consequential lack null mice −/− results increased freezing to shock a activity pattern basolateral complex amygdala. This is accompanied by altered transmission as observed inhibitory postsynaptic currents principal nucleus, which may explain fear hyperlocomotion escape-like responses aversive inescapable contexts. In contrast, lifelong deficiency heterozygous Tph +/ − able be compensated through reduced nucleus amygdala based mRNA upregulation subdivisions dorsal raphe neurons. due shock. conclusion, our reflect characteristic syndromal dimensions panic disorder agoraphobia. Thus, risk for anxiety- disorders including comorbid agoraphobia absence GABAergic-dependent compensatory mechanisms