DRIVE TO SMOKE AND DOPAMINE BLOCKADE

尼古丁对中枢多巴胺能神经通路传递的增强作用 可能是促使吸烟行为的主要强化机制。 到 为了探索这种可能性，我们建议研究一组个体，即， 精神分裂症患者，吸烟率超过 是普通人群的两倍。 这种疾病的某些症状 被认为是由于多巴胺通路的功能障碍。治疗这种疾病的药物 障碍阻断多巴胺受体。 我们已经开发出可靠有效的尼古丁饥饿测量方法， 包括香烟自我管理会议，其中患者 重复测定两小时内呼出的一氧化碳， 自由获取香烟，以及允许吸烟的烟雾混合装置 患者选择他们喜欢的香烟中尼古丁浓度 抽烟 我们建议测量72名新入院的尼古丁饥饿感 精神分裂症患者在前瞻性无抗精神病药洗脱期， 在为期42天的双盲试验中， 比较三种不同剂量的多巴胺 受体阻滞剂氟哌啶醇 我们将研究尼古丁是否以及如何 与氟哌啶醇剂量和血浆水平相关的饥饿变化， 治疗反应的展开和锥体外系的发展 副作用. 在双盲氟哌啶醇剂量比较的两周内，我们还将 确定四种不同剂量水平的尼古丁 透皮贴剂（0、7、14或21 mg，以拉丁方给药 平衡顺序效应的设计） 精神病理学和锥体外系副作用 拟议的工作将实质上澄清是否过量吸烟 反映了他们治疗疾病或 抵消药物治疗的副作用 它还将 提供有关尼古丁与 多巴胺系统，这在其他人群中无法获得。

Nicotine's enhancement of transmission in central dopaminergic pathways may be a primary reinforcing mechanism which drives smoking behavior. To explore this possibility we propose to study a group of individuals, i.e., patients with schizophrenia, who have a prevalence of smoking more than twice that of the general population. Certain symptoms of this disorder are believed due to dysfunction in dopamine pathways. Drugs to treat this disorder block dopamine receptors. We have developed reliable and valid measures of nicotine hunger, including cigarette self-administration sessions in which patients have repeated determinations of expired carbon monoxide during two hours of free access to cigarettes, and a smoke-mixing device which permits patients to select their preferred nicotine concentrations in cigarette smoke. We propose to measure nicotine hunger in 72 newly admitted patients with schizophrenia during a prospective neuroleptic-free washout, and on three subsequent occasions during a 42 day double-blind trial comparing three pharmacologically distinct dose levels of the dopamine receptor blocker, haloperidol. We will examine whether, and how, nicotine hunger changes in relation to haloperidol dose and plasma level, the unfolding of therapeutic response, and the development of extrapyramidal side effects. Two weeks into the double-blind haloperidol dose comparison, we will also determine the effects of four different dose levels of nicotine transdermal patch (O, 7, 14, or 21 mg, administered in a Latin square design balanced for order effects) on positive and negative psychopathology and extrapyramidal side effects. The proposed work will substantially clarify whether the excess of smoking in these patients reflects their efforts to treat their disease or to counteract the unwanted effects of its pharmacotherapy. It will also provide important information about the relationships between nicotine and dopamine systems which could not be obtained in other populations.