期刊
ADDICTION BIOLOGY
卷 17, 期 6, 页码 1026-1035出版社
WILEY
DOI: 10.1111/j.1369-1600.2010.00264.x
关键词
Addiction; ERK1; 2; human; nicotine; phosphorylation; smoking
资金
- Interdisciplinary Center for Clinical research (IZKF), the Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Germany
- Deutsche Forschungsgemeinschaft (German Research Foundation) [Wi1316/9-1]
From studies in cultured cells and animal models, nicotine and alcohol are known to regulate extracellular signal-regulated kinase 1 and 2 (ERK1/2). Alterations of ERK1/2 are thought to contribute to the drugs' rewarding effects. Accumulating evidence supports the importance of ERK1/2 in the molecular pathophysiology of depression and affective regulation in the hippocampus. We recently showed that the expression and phosphorylation of cyclic adenosine monophosphate response element (CRE)-binding protein (CREB) in human buffy coat were associated with smoking behavior. Because ERK1/2 is known to effect phosphorylation of CREB, the aim of the present study was to further elucidate whether cigarette smoking leads to alterations in terms of ERK1/2 in human buffy coat as well. In a comparison of 53 smokers with 146 non-smoking controls, we found significantly higher levels of ERK1/2 protein (P = 0.004). In contrast, phospho-ERK1/2, phospho-/total-ERK1/2 ratio, mRNA-ERK1 and mRNA-ERK2 were not significantly different. Multiple regression analysis revealed a significant relation among the number of cigarettes smoked daily (R2 = 0.266, P = 0.003), the Fagerstrom Test for Nicotine Dependence score (R2 = 0.149, P = 0.032) and the mRNA expression of ERK1. Moreover, our analysis suggests that the mRNA expression of ERK2 might be linked to mood (model summary: R2 = 0.087, P = 0.019; mRNA-ERK2: P = 0.026). Given that the ERK1/2 signaling pathway plays an important role in the physiology and pathophysiology of affective and addictive behavior, our findings provide a rationale basis for additional mechanistic studies that may lead to the development of novel signaling pathway selective therapeutics in humans.
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