Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Psychopharmacology (Berl). 2013 Sep;229(1):31-40. doi: 10.1007/s00213-013-3081-1. Epub 2013 Apr 19.
Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) α3-subunit (CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence.
We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI.
We assessed the effect of nicotine on PPI, startle reactivity, and habituation in 52 healthy nonsmoking volunteers genotyped for CHRNA3 rs1051730 in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Additionally, cotinine plasma levels were measured.
Nicotine significantly enhanced PPI in TT homozygotes only and tended to worsen PPI in TC and CC carriers. Additionally, nicotine significantly reduced startle habituation.
The present findings imply that the effect of nicotine on sensorimotor gating is modulated by nAChR α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior.
听觉惊跳反应的预脉冲抑制（PPI）是一种感觉运动门控的测量方法，可被尼古丁增强。此外，先前已经发现烟碱型乙酰胆碱受体（nAChR）α3 亚基（CHRNA3）rs1051730 多态性的 TT 基因型与 PPI 降低和尼古丁依赖有关。
我们测试了这种 CHRNA3 多态性是否也调节了尼古丁诱导的 PPI 增强。
我们在一项双盲、安慰剂对照、平衡、自身对照的设计中，评估了尼古丁对 52 名健康非吸烟志愿者的 PPI、惊跳反应和习惯化的影响，这些志愿者根据 CHRNA3 rs1051730 进行了基因分型。此外，还测量了可替宁的血浆水平。
尼古丁仅在 TT 纯合子中显著增强了 PPI，而在 TC 和 CC 携带者中则倾向于恶化 PPI。此外，尼古丁显著降低了惊跳反应的习惯化。
目前的研究结果表明，尼古丁对感觉运动门控的影响受到 nAChR α3 亚单位的调节。因此，烟碱受体基因的遗传变异可能是早期注意过程和吸烟行为之间的重要连接环节。
