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Chronic isolation stress alters antidepressant‐like behaviors in animals lacking RGS4
Author(s) -
Talbot Jeffery N,
Leon Bernice Poncede,
Nielsen Cienna L,
Benhatzel Christopher M,
Alp Deniz,
Kirsh Robert,
Traynor John R
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.929.6
Subject(s) - antidepressant , serotonin , mood , mood disorders , psychology , chronic stress , pharmacology , behavioural despair test , neuroscience , biology , medicine , psychiatry , receptor , hippocampus , anxiety
Conventional treatments for depression increase serotonin (5‐HT) levels with selective serotonin reuptake inhibitors (SSRIs). Although superior to previous treatments, SSRIs cause unpleasant side effects, are ineffective in many patients, and take weeks to months for therapeutic benefit pointing to the need for improved understanding of mechanisms regulating mood and antidepressant drug action. Evidence suggests that antidepressant behaviors and more specifically the antidepressant actions of serotonin (5‐HT) are modulated by endogenous regulators of G protein signaling (RGS) proteins. In the current study, the effects of chronic isolation stress on mood‐related behaviors of mice lacking RGS4 were tested. Genetic deletion of RGS4 (RGS4 (−/−) ) had no effect on basal antidepressant‐like behaviors or generalized locomotor activity in mice. However, when subjected to chronic isolation stress, RGS4 (−/−) mice developed antidepressant‐like phenotypes whereas unstressed RGS4 (−/−) animals exhibited basal behaviors similar to stressed and unstressed wild‐type (RGS4 (+/+) ) littermates. Moreover, chronically‐stressed RGS4 (−/−) animals exhibited increased phosphorylation of neuronal GSK3β, a putative biological marker of antidepressant‐like activity. Importantly, RGS4 deletion suppressed SSRI‐induced antidepressant activity but had no effect on basal or drug‐induced locomotor activity. Overall, these data suggest chronic stress differentially influences antidepressant‐like behaviors in an RGS4‐dependant manner and point to a role for RGS4 in the regulation of mood‐related behavior in vivo. Support or Funding Information Supported by MH0907012.