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

摘要

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 neurotransmis-sion, 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.