Wescott Seth A, Ronan Elizabeth A, Xu X Z Shawn
aNeuroscience Graduate Program bLife Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Behav Pharmacol. 2016 Feb;27(1):44-9. doi: 10.1097/FBP.0000000000000186.
Insulin signaling has been suggested to modulate nicotine dependence, but the underlying genetic evidence has been lacking. Here, we used the nematode, Caenorhabditis elegans, to investigate whether genetic alterations in the insulin signaling pathway affect behavioral responses to nicotine. For this, we challenged drug-naive C. elegans with an acute dose of nicotine (100 μmol/l) while recording changes in their locomotion speed. Although nicotine treatment stimulated locomotion speed in wild-type C. elegans, the same treatment reduced locomotion speed in mutants defective in insulin signaling. This phenotype could be suppressed by mutations in daf-16, a gene encoding a FOXO transcription factor that acts downstream of insulin signaling. Our data suggest that insulin signaling genes, daf-2, age-1, pdk-1, akt-1, and akt-2, modulate behavioral responses to nicotine in C. elegans, indicating a genetic link between nicotine behavior and insulin signaling.
胰岛素信号传导被认为可调节尼古丁依赖，但相关遗传学证据一直缺乏。在此，我们利用线虫秀丽隐杆线虫来研究胰岛素信号通路中的基因改变是否会影响对尼古丁的行为反应。为此，我们用急性剂量的尼古丁（100 μmol/l）刺激未接触过药物的秀丽隐杆线虫，同时记录其运动速度的变化。虽然尼古丁处理能刺激野生型秀丽隐杆线虫的运动速度，但相同处理却降低了胰岛素信号传导缺陷型突变体的运动速度。该表型可被daf-16基因的突变所抑制，daf-16是一个编码FOXO转录因子的基因，在胰岛素信号传导下游起作用。我们的数据表明，胰岛素信号传导基因daf-2、age-1、pdk-1、akt-1和akt-2可调节秀丽隐杆线虫对尼古丁的行为反应，表明尼古丁行为与胰岛素信号传导之间存在遗传联系。
