Oral Presentation The International Congress of Neuroendocrinology 2014

Inescapable tail shock increases tph2 mRNA and Tph2 protein selectively in the dorso-caudal dorsal raphe nucleus, and interacts with cold swim stress to cause a proinflammatory cytokine milieu and depressive-like behavior (#90)

Nina C Donner 1 2 , Kenneth H Kubala 1 , Robert C Drugan 3 , Steven F Maier 1 , Christopher A Lowry 1
  1. University of Colorado Boulder, Boulder, Colorado, USA
  2. Max Planck Institute of Psychiatry, Munich, Bavaria, Germany
  3. University of New Hampshire, Durham, NH, USA

Expression of TPH2, the gene encoding the rate-limiting enzyme for brain serotonin synthesis, is elevated in the dorso-caudal subdivision of the dorsal raphe nucleus (cDRD) of depressed suicide victims, but the underlying mechanisms are still unclear. One hypothesis is that certain stressors (depending on stressor type, severity, duration and sequence/interaction) are sufficient to elevate TPH2 expression. We hypothesized that exposure to an acute stressor in adult male rats, namely one session of intermittent tail shocks (IS, 90 min), is sufficient to increase tph2 mRNA and Tph2 protein expression, and to sensitize the DR to a subsequent, heterotypic stressor. We measured tph2 mRNA expression 4 h after IS or home cage control (HC) conditions (Experiment 1), and following IS versus HC conditions on day 1 and cold swim stress (10 min, 15 ºC) or HC conditions 24 h later (Experiment 2). In a time course study (Experiment 3), we also measured Tph2 protein expression 12 and 24 h after IS using western blot. Inescapable shock, but not cold swim stress, was sufficient to increase tph2 mRNA 4 h after the onset of IS, and Tph2 protein expression 24 h after onset of IS, both selectively in the cDRD. Furthermore, IS was permissive for cold swim-induced increases in tph2 mRNA expression 24 h later, again selectively in the cDRD, associated with increased immobility during the cold swim exposure and a proinflammatory plasma cytokine milieu (IL-6/IL-10 ratio). Plasma corticosterone remained elevated 24 h following IS, and 4 h following cold swim stress irrespective of prior stress exposure (IS or HC). These data demonstrate that IS is sufficient to increase tph2 mRNA and Tph2 protein expression selectively in the cDRD, a serotonergic subdivision that is heavily innervated and controlled by the medial prefrontal cortex, and sensitizes cDRD serotonergic neurons to a subsequent, heterotypic stressor.