Division of Substance Abuse, Department of Psychiatry, Yale University School of Medicine, 2 Church St South, Suite 109, New Haven, CT 06519, United States.
Schizophr Res. 2009 Dec;115(2-3):317-24. doi: 10.1016/j.schres.2009.07.019. Epub 2009 Aug 22.
Individuals with schizophrenia have higher plasma nicotine levels in comparison to non-psychiatric smokers, even when differences in smoking are equated. This difference may be related to how intensely cigarettes are smoked but this has not been well studied. Mecamylamine (MEC), a non-competitive nicotinic acetylcholine receptor (nAChR) antagonist, which has been shown to increase ad-lib smoking and to affect smoking topography, was used in the current study as a pharmacological probe to increase our understanding of smoking behavior, smoking topography, and resulting nicotine levels in smokers with schizophrenia. This preliminary study used a within-subject, placebo-controlled design in smokers with schizophrenia (n=6) and healthy control smokers (n=8) to examine the effects of MEC (10mg/day) on ad-lib smoking behavior, topography, nicotine levels, and tobacco craving across two smoking deprivation conditions (no deprivation and 12-h deprivation). MEC, compared to placebo, increased the number of cigarettes smoked and plasma nicotine levels. MEC increased smoking intensity and resulted in greater plasma nicotine levels in smokers with schizophrenia compared to controls, although these results were not consistent across deprivation conditions. MEC also increased tobacco craving in smokers with schizophrenia but not in control smokers. Our results suggest that antagonism of high-affinity nAChRs in smokers with schizophrenia may prompt compensatory smoking, increasing the intensity of smoking and nicotine exposure without alleviating craving. Further work is needed to assess whether nicotine levels are directly mediated by how intensely the cigarettes are smoked, and to confirm whether this effect is more pronounced in smokers with schizophrenia.
与非精神病吸烟者相比，精神分裂症患者的血浆尼古丁水平更高，即使在吸烟差异相等的情况下也是如此。这种差异可能与香烟的吸食强度有关，但目前对此研究甚少。美加仑胺（MEC）是非竞争性烟碱型乙酰胆碱受体（nAChR）拮抗剂，已被证明可增加随意吸烟量并影响吸烟模式，目前被用于本研究中，以增加我们对吸烟行为、吸烟模式以及精神分裂症吸烟者尼古丁水平的理解。这项初步研究采用了精神分裂症吸烟者（n=6）和健康对照组吸烟者（n=8）的个体内、安慰剂对照设计，以检查 MEC（10mg/天）对随意吸烟行为、吸烟模式、尼古丁水平和烟草渴求的影响，共进行了两种吸烟剥夺条件（不剥夺和 12 小时剥夺）。与安慰剂相比，MEC 增加了吸烟量和血浆尼古丁水平。MEC 增加了吸烟强度，并导致精神分裂症吸烟者的血浆尼古丁水平高于对照组，尽管这些结果在剥夺条件之间并不一致。MEC 还增加了精神分裂症吸烟者的烟草渴求，但对对照组吸烟者没有影响。我们的研究结果表明，在精神分裂症吸烟者中阻断高亲和力烟碱型乙酰胆碱受体可能会促使补偿性吸烟，增加吸烟强度和尼古丁暴露量，而不会减轻烟瘾。需要进一步研究来评估尼古丁水平是否直接受到吸烟强度的影响，并确认这种影响在精神分裂症吸烟者中是否更为明显。
