CHOLINERGIC/BETA-ENDORPHINERGIC REINFORCEMENT OF SMOKING

尼古丁刺激香烟释放神经肽的研究 吸烟暗示了积极强化或奖励的机制 这些过程可能解释了对吸烟的歧视性控制， 尼古丁成瘾循环的刺激依赖。 我们将试图 通过实验证明，使用行为标记和生物化学 测量，一种神经肽-β-内啡肽-对 吸烟的强化。 基本方法包括 重复测量的主题设计，不同的实验 连续几天研究的条件和同时测量 主观、行为、生理和生化变量。 的 研究的具体目的是：（一）证明 吸烟引起的尼古丁摄入对相关行为指标的影响 胆碱能/β-内啡肽能活性（冷水疼痛和困惑 焦虑）; II）以确定是否疼痛减轻（抗伤害感受）， 吸烟是由于尼古丁戒断的终止或尼古丁 独立于撤回的影响;三）确定是否频率 或吸烟的强度因烦躁状态而增加， 与尼古丁成瘾周期相关，如焦虑; IV）排序 烟碱胆碱能活性的相对贡献， β-内啡肽能活性对疼痛和焦虑反应通过 给予胆碱能阻滞剂（美加明）、阿片类药物 拮抗剂（纳洛酮）或合成β-内啡肽。 该项目有其 长期研究目标：行为（心理） 尼古丁与吸烟的生化（神经内分泌）研究 和精神药理学）的神经肽活性的研究， 正常的人类水平。 对健康的影响是， 吸烟和药物滥用的潜在生物行为机制可能 使合理治疗的发展成为可能， 比目前的有效性。

Investigations on nicotine-stimulated neuropeptide release from cigarette smoking suggest mechanisms involving positive reinforcement or rewarding processes which might explain the discriminative control of smoking by stimuli dependent of the nicotine-addiction cycle. We shall attempt to demonstrate experimentally, using behavioral markers and biochemical measurements, the contribution of one neuropeptide -- Beta-endorphin -- to the reinforcement of smoking. The basic approach involves a repeated-measures within subjects design, with different experimental conditions studied over successive days and simultaneous measurement of subjective, behavioral, physiological, and biochemical variables. The specific aims of the research are: I) to demonstrate the effects of nicotine intake from smoking on relevant behavioral markers of cholinergic/Beta-endorphinergic activity (cold-water pain and puzzle anxiety); II) to determine whether pain-reduction (antinociception) from smoking is due to the termination of nicotine-withdrawal or to nicotine effects independent of withdrawal; III) to establish whether the frequency or intensity of cigarette smoking is increased by a dysphoric state not associated with the nicotine-addiction cycle, such as anxiety; IV) to sort out the relative contribution of nicotinic cholinergic activity and Beta-endorphinergic activity on pain and anxiety responses through the administration of a cholinergic blocker (mecamylamine), an opiate antagonist (naloxone), or synthetic Beta-endorphin. The project has its long-term research objective the integration of behavioral (psychological) research on nicotine and smoking with biochemical (neuroendocrinological and psychopharmacological) investigations of neuropeptide activity at the normal human level. The health implicatons are that a better understanding of underlying biobehavioral mechanisms in smoking and substance abuse may make possible the development of rational therapies of greater effectiveness than are currently available.