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RGS4 as a regulator of the antidepressant effects of SSRIs
Author(s) -
Amos Mary Ellen,
Binkey Amanda E.,
Taylor Phillip N.,
Rorabaugh Boyd R.,
Neubig Richard R.,
Traynor John R.,
Talbot Jeffery N.
Publication year - 2012
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.26.1_supplement.1045.6
Subject(s) - desipramine , downregulation and upregulation , endocrinology , medicine , serotonin , antidepressant , reuptake inhibitor , behavioural despair test , serotonin reuptake inhibitor , fluoxetine , chemistry , pharmacology , hippocampus , biology , receptor , gene , biochemistry
Previously, we showed that RGS‐insensitive Gαi2 G184S (Gαi2 GS ) mice exhibit basal and serotonin‐dependent antidepressant (AD) phenotypes. Here we show that acute (3‐day) administration of the serotonin selective reuptake inhibitor (SSRI) fluoxetine (FLX) produced AD‐like responses in Gαi2 GS mice in the novelty‐induced hypophagia test, which requires chronic (21‐day) FLX to produce AD effects in wild‐type (WT) animals. In contrast, acute desipramine, a norepinephrine‐based antidepressant, had no effect. The AD efficacy of FLX in acutely treated Gαi2 GS mice was twice that of chronically treated WT littermates. Also, Gαi2 GS mice exhibited basal and selective 4‐fold upregulation of cortical RGS4 vs. WT mice. mRNA expression of eleven RGS proteins in the cortex and hippocampus by RT‐PCR showed chronic FLX selectively upregulated cortical RGS4 in WT mice. Notably, vehicle‐treated Gαi2 GS mice showed similar regional and RGS‐selective upregulation of cortical RGS4 mRNA and protein. These are the first studies of which we are aware to show altered expression of RGS proteins in response to SSRIs. Overall, these data suggest RGS insensitivity improves the efficacy and onset of action of SSRIs in animal models of mood. Moreover, upregulation of cortical RGS4 may contribute to the AD phenotype of Gαi2 GS animals and to the therapeutic effects of SSRIs. Supported by DA04087 and the Bower Bennett Bennett Endowment.