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

Abstract

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.

Heavy Smoking is Associated with Low Depression and Stress: a Smokers' Paradox in Cardiovascular Disease?

“…the satisfaction derived from smoking and alleviation of withdrawal symptoms-may account for this apparently paradoxical result. In other words, smokers may misattribute the relief of withdrawal symptoms as reflecting a genuine antidepressant and anxiolytic effect of nicotine dependence (17)(18)(19). Indeed, nicotine has to some extent antidepressant activity which is explained by the fact that the long-term antidepressant activity of any drug appears to depend on its ability to modulate changes in the dopamine, norepinephrine and serotonin.…”

“…Indeed, nicotine has to some extent antidepressant activity which is explained by the fact that the long-term antidepressant activity of any drug appears to depend on its ability to modulate changes in the dopamine, norepinephrine and serotonin. Furthermore, as a major psychoactive component of tobacco nicotine produces both anxiolytic and antidepressant like effects in both humans and animals (18)(19). However, co-occurring depressive symptoms and smoking do not appear to synergistically convey risk for cardiovascular disease (7).…”

“…However, co-occurring depressive symptoms and smoking do not appear to synergistically convey risk for cardiovascular disease (7). Additionally, the relationship between nicotine dependence, anxiety and depression may be bidirectional with smoking initially used to alleviate symptoms but in fact worsening them over time as it dysregulates the hypothalamic-pituitary-adrenal system and results in hypersecretion of cortisol which in turn influences reactions to environmental stressors (17)(18)(19).…”

Biomarker discovery in attention deficit hyperactivity disorder: RNA sequencing of whole blood in discordant twin and case-controlled cohorts

“…RGS2 has diverse actions including promoting the translation of stress-associated proteins ATF4 and CHOP via an eIF-2B inhibitory domain [ 53 ]. Of potential importance, RGS2 variants have been associated with childhood adversities as predictors of anxious and depressive responses [ 54 ], as well as the regulation of nicotine-induced anxiolytic activity in mice, and cocaine-induced rewarding effects [ 55 , 56 ]. Likewise, RGS2 is thought to mediate the anxiolytic effects of oxytocin [ 57 ], and affects T cell activation, anxiety, and male aggressive behavior [ 58 ].…”

Dietary, physical exercises and mental stress in a Chinese population: a cross-sectional study

“…Hence, the link between drinking alcohol and mental stress seems complex and requires to be elucidated in more detailed and specific researches. And nicotine, as the major psychoactive component, has antidepressant and anxiolytic activity in both animals and humans [ 52 , 53 ], which explained the fact that the negative relationship high smoking and mental stress for males to some extent.…”