Regulator of G protein signaling 2 differentially regulates nicotine‐induced anxiolytic‐ and antidepressant‐like effects in mice

This study assessed the role of regulator of G protein signaling 2 (RGS2) in nicotine‐induced anxiolytic‐ and antidepressant‐like effects using RGS2 wildtype (WT) and RGS2 knockout (KO) mice. RGS2 negatively regulates monoaminergic neurotransmission, which is implicated in the pathology of anxiety and depression. We hypothesized that deletion of RGS2 would enhance nicotine‐induced anxiolytic‐ and antidepressant‐like effects, which were assessed using the elevated plus maze and tail suspension tests, respectively. Anxiolytic‐like effects were observed in both RGS2 WT and KO mice after administration of low dose of nicotine (0.05 mg/kg, base) compared to respective saline controls. Additionally, administration of nicotine (0.1 mg/kg, base) compared to saline resulted in anxiolytic‐like effects in RGS2 KO mice, but not RGS2 WT mice, suggesting genetic deletion of RGS2 facilitated anxiolytic‐like effects of nicotine. Administration of nicotine (0.5 and 1 mg/kg, base) compared to saline resulted in antidepressant‐like effects in RGS2 WT mice. Antidepressant‐like effects were observed in RGS2 KO mice only at the highest tested dose of nicotine (1 mg/kg, base) compared to saline controls, suggesting that genetic deletion of RGS2 decreased sensitivity to antidepressant‐like effects of nicotine. Together, the data suggest that RGS2 differentially regulated nicotine‐induced affective behavioral responses. These data suggest that individuals with RGS2 polymorphisms may experience differential affective responses to tobacco smoking, which may make them vulnerable to developing nicotine addiction. The study assessed the anxiolytic‐ and antidepressant‐like effects of nicotine in mice possessing or lacking regulator of G‐protein signaling 2 (RGS2). The primary finding of this study is that nicotine‐induced anxiolytic‐like effects were facilitated in the absence of RGS2. In contrast, sensitivity to the antidepressant‐like effects of nicotine were decreased in the absence of RGS2. RGS2 did not influence nicotine‐induced locomotor activity.