Genetically driven brain serotonin deficiency facilitates panic-like escape behavior in mice
Waider J., Popp S., Lange M. D., Kern R., Kolter J. F., Kobler J., Donner N. C., Lowe K. R., Malzbender J. H., Brazell C. J., Arnold M. R., Aboagye B., Schmitt-Böhrer A., Lowry C. A., Pape H. C., Lesh K. Yu.
Translational Psychiatry
Vol.7, Issue10, P. e1246
Опубликовано: 2017
Тип ресурса: Статья
Аннотация:
Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings. Our findings indicate that constitutive Tph2 inactivation and consequential lack of 5-HT synthesis in Tph2 null mutant mice (Tph2-/-) results in increased freezing to associated foot shock and a differential c-Fos activity pattern in the basolateral complex of the amygdala. This is accompanied by altered GABAergic transmission as observed by recordings of inhibitory postsy
Ключевые слова:
4 aminobutyric acid; serotonin; serotonin transporter; Slc6a4 protein, mouse; Tph2 protein, mouse; tryptophan hydroxylase; agoraphobia; amygdala; animal; anxiety; deficiency; electric shock; escape behavior; fear; genetics; inhibitory postsynaptic potential; knockout mouse; male; metabolism; panic; pathophysiology; physiology; raphe nucleus; Agoraphobia; Amygdala; Animals; Anxiety; Electroshock; Escape Reaction; Fear; gamma-Aminobutyric Acid; Inhibitory Postsynaptic Potentials; Male; Mice, Knockout; Panic Disorder; Raphe Nuclei; Serotonin; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase
Язык текста: Английский
ISSN: 2158-3188
Waider J.
Popp S.
Lange M. D.
Kern R.
Kolter J. F.
Kobler J.
Donner N. C.
Lowe K. R.
Malzbender J. H.
Brazell C. J.
Arnold M. R.
Aboagye B.
Schmitt-Böhrer A.
Lowry C. A.
Pape H. C.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Wаидер Й.
Попп С.
Ланге М. Д.
Керн Р.
Колтер Й. Ф.
Коблер Й.
Доннер Н. C.
Лоwе К. Р.
Малзбендер Й. Х.
Бразелл C. Й.
Арнолд М. Р.
Абоагье Б.
Счмитт-Бöхрер А.
Лоwрy C. А.
Папе Х. C.
Леш К. Ю. Клаус-Петер Юлиус 1957-
Genetically driven brain serotonin deficiency facilitates panic-like escape behavior in mice
Текст визуальный непосредственный
Translational Psychiatry
Vol.7, Issue10 P. e1246
2017
Статья
4 aminobutyric acid serotonin serotonin transporter Slc6a4 protein, mouse Tph2 protein, mouse tryptophan hydroxylase agoraphobia amygdala animal anxiety deficiency electric shock escape behavior fear genetics inhibitory postsynaptic potential knockout mouse male metabolism panic pathophysiology physiology raphe nucleus Agoraphobia Amygdala Animals Anxiety Electroshock Escape Reaction Fear gamma-Aminobutyric Acid Inhibitory Postsynaptic Potentials Male Mice, Knockout Panic Disorder Raphe Nuclei Serotonin Serotonin Plasma Membrane Transport Proteins Tryptophan Hydroxylase
Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings. Our findings indicate that constitutive Tph2 inactivation and consequential lack of 5-HT synthesis in Tph2 null mutant mice (Tph2-/-) results in increased freezing to associated foot shock and a differential c-Fos activity pattern in the basolateral complex of the amygdala. This is accompanied by altered GABAergic transmission as observed by recordings of inhibitory postsy