title: Stressor-like effects of c-Jun N-terminal kinase (JNK) inhibition.
abstract: There is an urgent need for novel treatment strategies for stressor related disorders, particularly depression and anxiety disorders. Indeed, existing drug treatments are only clinically successful in a subset of patients and relapse is common. This likely stems from the fact that stressor disorders are heterogeneous with multiple biological pathways being affected. To this end, the present investigation sought to assess in mice the contribution of the c-Jun N terminal kinase (JNK) pathway to the behavioral, hormonal and neurochemical effects of an acute stressor. Indeed, although JNK has been shown to modulate glucocorticoid receptors in vitro, virtually nothing is known of the role for JNK in affecting stressor induced pathology. We presently found that the JNK antagonist, SP600125, (but not the p38 antagonist, SB203580) increased plasma corticosterone levels under resting conditions and in the context of an acute stressor (wet bedding + restraint). SP600125 also reduced exploration in an open field arena, but prevented the stressor induced increase in open arm exploration in an elevated plus maze. Finally, SP600125 affected noradrenergic activity in the central amygdala and locus coruleus under resting condition, but prevented the noradrenergic effects within the paraventricular nucleus of the hypothalamus that were induced by the acute stressor exposure. These data suggest inhibiting endogenous JNK can have stressor-like corticoid, behavioral and central monoamine effects under basal conditions, but can actually reverse some behavioral and neurochemical effects of an acute stressor. Thus, endogenous JNK appears to affect stress relevant processes in a context-dependent manner.
authors.affiliation: Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Clarke
authors.forename: Rowan
authors.initials: R
authors.lastname: Pentz
authors.forename: Jessica
authors.initials: J
authors.lastname: Bobyn
authors.forename: Shawn
authors.initials: S
authors.lastname: Hayley
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D015153:Blotting, Western; D003345:Corticosterone / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects*
chemical_list: D000873:Anthracenes; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D003345:Corticosterone; D009638:Norepinephrine