RT Journal Article
SR Electronic
T1 Striatal RGS7 regulates depression-related behaviors and stress-induced reinstatement of cocaine conditioned place preference
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0365-20.2020
DO 10.1523/ENEURO.0365-20.2020
A1 Laurie P. Sutton
A1 Natalia Khalatyan
A1 Jeffrey N. Savas
A1 Kirill A. Martemyanov
YR 2021
UL http://www.eneuro.org/content/early/2021/01/04/ENEURO.0365-20.2020.abstract
AB The striatum plays a key role in both reward-related and affective behaviors and disruptions to this circuit contributes to depression and drug addiction. However, our understanding of the molecular factors that facilitate and modify these processes are incomplete. Striatal function is modulated by G protein coupled receptors (GPCRs) that process vast neuromodulatory inputs. GPCR signaling is negatively regulated by Regulator of G protein Signaling (Rgs) proteins. In this study, we examine the role of striatal Rgs proteins in depressive-like and reward-related behaviors in male mice. Using a genetic mouse model with specific elimination of Rgs7 in striatal neurons we found that these mice exhibit an anxiolytic-like and antidepressant-like phenotype. In contrast, knockout of Rgs9, an abundant Rgs protein in the same neuronal population did not affect the behavioral outcome in the depressive-like tests. Mice lacking striatal Rgs7 did not show significant differences in cocaine-induced psychomotor activation, sensitization or conditional place preference (CPP). Interestingly, loss of Rgs7 in the striatum made mice resilient to stress-induced but not drug-induced reinstatement of cocaine CPP. Analysis of striatal proteome revealed that loss of Rgs7 selectively affected expression of several networks, most prominently including proteins involved in translation and vesicular exocytosis. Together, these findings begin to demonstrate the specific contribution of Rgs7 acting in the striatum towards depression as it relates to stress-induced reinstatement of drug use.SIGNIFICANCE STATEMENT G protein coupled receptors (GPCRs) play a key role in modulating responses of striatal neurons that ultimately shape complex behaviors such as mood and reward. The extent of GPCR signaling is tightly controlled by Regulators of G protein signaling (Rgs). In this study, we report a key role of Rgs7 in the striatum towards depression and reward-related behaviors, while addressing the effects of stress on these behavioral outcomes. Together our findings provide new insights into the molecular mechanisms involved in stress induced drug seeking behaviors.