Citation

Donner NC, Kubala KH, Hassell JE, Lieb MW, Nguyen KT, Heinze JD, Drugan RC, Maier SF, Lowry CA. Neurobiol. Stress 2018; 8: 68-81.

Copyright

(Copyright © 2018, Elsevier Publishing)

DOI

10.1016/j.ynstr.2018.01.003

PMID

unavailable

Abstract

Expression of TPH2, the rate-limiting enzyme for brain serotonin synthesis, is elevated in the dorsal raphe nucleus (DR) of depressed suicide victims. One hypothesis is that this increase in TPH2 expression is stress-induced. Here, we used an established animal model to address whether exposure to an acute stressor, inescapable tail shock (IS), increases tph2 mRNA and Tph2 protein expression, and if IS sensitizes the DR to a subsequent, heterotypic stressor. In Experiment 1, we measured tph2 mRNA expression 4 h after IS or home cage (HC) control conditions in male rats, using in situ hybridization histochemistry. In Experiment 2, we measured Tph2 protein expression 12 h or 24 h after IS using western blot. In Experiment 3, we measured tph2 mRNA expression following IS on Day 1, and cold swim stress (10 min, 15 °C) on Day 2. Inescapable tail shock was sufficient to increase tph2 mRNA expression 4 h and 28 h later, selectively in the dorsomedial DR (caudal aspect of the dorsal DR, cDRD; an area just rostral to the caudal DR, DRC) and increased Tph2 protein expression in the DRD (rostral and caudal aspects of the dorsal DR combined) 24 h later. Cold swim increased tph2 mRNA expression in the dorsomedial DR (cDRD) 4 h later. These effects were associated with increased immobility during cold swim, elevated plasma corticosterone, and a proinflammatory plasma cytokine milieu (increased interleukin (IL)-6, decreased IL-10). Our data demonstrate that two models of inescapable stress, IS and cold swim, increase tph2 mRNA expression selectively in the anxiety-related dorsomedial DR (cDRD). © 2018 The Authors

Language: en

Keywords

adult; Anxiety; male; Inflammation; anxiety; stress; controlled study; priority journal; nonhuman; messenger RNA; animal experiment; animal model; rat; protein expression; Article; animal tissue; dorsal raphe nucleus; autoradiography; Western blotting; Tryptophan hydroxylase; in situ hybridization; tryptophan hydroxylase 2; Dorsal raphe nucleus; forced swim test; cold swim test; dorsomedial hypothalamic nucleus; experimental test; histochemistry; Inescapable stress