Perkins Kenneth A, Lerman Caryn, Grottenthaler Amy, Ciccocioppo Melinda M, Milanak Melissa, Conklin Cynthia A, Bergen Andrew W, Benowitz Neal L
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Behav Pharmacol. 2008 Sep;19(5-6):641-9. doi: 10.1097/FBP.0b013e32830c367c.
Negative mood increases smoking reinforcement and risk of relapse. We explored associations of gene variants in the dopamine, opioid, and serotonin pathways with smoking reward ('liking') and reinforcement (latency to first puff and total puffs) as a function of negative mood and expected versus actual nicotine content of the cigarette. Smokers of European ancestry (n=72) were randomized to one of four groups in a 2x2 balanced placebo design, corresponding with manipulation of actual (0.6 vs. 0.05 mg) and expected (told nicotine and told denicotinized) nicotine 'dose' in cigarettes during each of two sessions (negative vs. positive mood induction). Following mood induction and expectancy instructions, they sampled and rated the assigned cigarette, and then smoked additional cigarettes ad lib during continued mood induction. The increase in smoking amount owing to negative mood was associated with: dopamine D2 receptor (DRD2) C957T (CC>TT or CT), SLC6A3 (presence of 9 repeat>absence of 9), and among those given a nicotine cigarette, DRD4 (presence of 7 repeat>absence of 7) and DRD2/ANKK1 TaqIA (TT or CT>CC). SLC6A3, and DRD2/ANKK1 TaqIA were also associated with smoking reward and smoking latency. OPRM1 (AA>AG or GG) was associated with smoking reward, but SLC6A4 variable number tandem repeat was unrelated to any of these measures. These results warrant replication but provide the first evidence for genetic associations with the acute increase in smoking reward and reinforcement owing to negative mood.
消极情绪会增加吸烟的强化作用和复发风险。我们探讨了多巴胺、阿片类和血清素途径中的基因变异与吸烟奖励（“喜好”）和强化作用（首次抽吸潜伏期和总抽吸次数）之间的关联，这些关联是消极情绪以及香烟预期与实际尼古丁含量的函数。欧洲血统的吸烟者（n = 72）在2×2平衡安慰剂设计中被随机分为四组，这与在两个阶段（消极情绪与积极情绪诱导）中对香烟实际（0.6毫克与0.05毫克）和预期（告知含尼古丁与告知去尼古丁）尼古丁“剂量”的操纵相对应。在情绪诱导和预期指导之后，他们对分配的香烟进行抽样并评分，然后在持续的情绪诱导期间随意吸食更多香烟。消极情绪导致的吸烟量增加与以下因素有关：多巴胺D2受体（DRD2）C957T（CC>TT或CT）、SLC6A3（存在9次重复>不存在9次重复），以及在吸食尼古丁香烟的人群中，DRD4（存在7次重复>不存在7次重复）和DRD2/ANKK1 TaqIA（TT或CT>CC）。SLC6A3和DRD2/ANKK1 TaqIA也与吸烟奖励和吸烟潜伏期有关。OPRM1（AA>AG或GG）与吸烟奖励有关，但SLC6A4可变数目串联重复与这些指标均无关。这些结果有待重复验证，但为基因与因消极情绪导致的吸烟奖励和强化作用急性增加之间的关联提供了首个证据。
