Role of Regulator of G-protein Signaling 4 Protein in Antidepressant Effects of Nicotine and Conventional Antidepressants

Tobacco smoking is commonly seen amongst patients suffering from depression. Comorbid depression in smokers can make quitting tobacco smoking difficult. In addition, patients with depression can have severe withdrawal symptoms upon quitting smoking. Identifying factors that promote depression and increase susceptibility to tobacco smoking will help in treating both depression and promote smoking cessation. Nicotine, the major psychoactive component of tobacco smoke, causes dopamine release which mediates its antidepressant effects. Dopamine also plays a role in mediating depression. The regulator of G-protein signaling 4 (RGS4) protein has been linked to dopamine regulation by inhibiting the effects of dopamine receptor activation. The purpose of this study is to assess the antidepressant effects of nicotine in RGS4 knockout and wildtype mice. The depression-like behaviors will be assessed using the tail suspension model. In addition, we will assess effects of conventional antidepressant such as fluoxetine, bupropion and desipramine in both RGS4 knockout and wildtype mice. We hypothesize that RGS4 knockout mice will be more sensitive to the antidepressant effects of nicotine and conventional antidepressant medications. The data are currently being analyzed. This research work will help elucidate the role of RGS4 in both depression and nicotine addiction.