Differential responses to anxiogenic drugs in a mouse model of panic disorder as revealed by Fos immunocytochemistry in specific areas of the fear circuitry |
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Authors: | I. Sahún X. Gallego M. Gratacòs P. Murtra R. Trullás R. Maldonado X. Estivill M. Dierssen |
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Affiliation: | (1) Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain;(2) Unit of Neuropharmacology, Pompeu Fabra University, Barcelona, Spain;(3) Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain;(4) Neurobiology Unit, Institut d’Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain;(5) Genetics Unit, Pompeu Fabra University, Barcelona, Spain |
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Abstract: | Summary. Sensitivity to pharmacological challenges has been reported in patients with panic disorder. We have previously validated transgenic mice overexpressing the neurotrophin-3 (NT-3) receptor, TrkC (TgNTRK3), as an engineered murine model of panic disorder. We could determine that TgNTRK3 mice presented increased cellularity in brain regions, such as the locus ceruleus, that are important neural substrates for the expression of anxiety in severe anxiety states. Here, we investigated the sensitivity to induce anxiety and panic-related symptoms by sodium lactate and the effects of various drugs (the α2-adrenoceptor antagonist, yohimbine and the adenosine antagonist, caffeine), in TgNTRK3 mice. We found enhanced panicogenic sensitivity to sodium lactate and an increased intensity and a differential pattern of Fos expression after the administration of yohimbine or caffeine in TgNTRK3. Our findings validate the relevance of the NT-3/TrkC system to pathological anxiety and raise the possibility that a specific set of fear-related pathways involved in the processing of anxiety-related information may be differentially activated in panic disorder. |
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Keywords: | : Panic disorder – Fos immunohistochemistry – Amygdala – Locus ceruleus – TrkC – NT-3 – Yohimbine – Caffeine |
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