University of Minnesota Medical School, Duluth, MN 55812, USA.
Pharmacol Biochem Behav. 2010 Mar;95(1):1-5. doi: 10.1016/j.pbb.2009.11.016. Epub 2009 Dec 5.
Endogenous opioids are integral in modulating drug reward, but it is believed that these may act through several mechanisms including hypothalamic-pituitary-adrenocortical (HPA) and dopamine pathways. This study was developed to examine how nicotine dependence alters endogenous opioid regulation of prolactin response, a peripheral marker of dopaminergic activity. Smokers and nonsmokers completed two sessions during which placebo or 50mg of naltrexone was administered, using a double-blind, counterbalanced design. Blood samples and mood measures were obtained during a resting absorption period, after exposure to two noxious stimuli (cold pressor and thermal pain), and during an extended recovery period. Opioid blockade increased prolactin response, indicating an inhibitory effect of the endogenous opioid system on prolactin, possibly mediated by reduced stimulatory effects of dopamine on this hormone. These responses were attenuated in smokers relative to nonsmokers. There was also a gender disparity in prolactin response, with women showing a stronger response to endogenous opioid modification than men regardless of smoking status. The attenuated effects of opioid blockade may reflect dysregulated opiodergic and dopaminergic effects. Results extend previous reports showing blunted opioid regulation of the HPA response in dependent smokers.
内源性阿片类物质在调节药物奖赏中起着重要作用，但据信它们可能通过多种机制起作用，包括下丘脑-垂体-肾上腺皮质（HPA）和多巴胺途径。这项研究旨在探讨尼古丁依赖如何改变内源性阿片类物质对催乳素反应的调节作用，催乳素反应是多巴胺活性的外周标志物。吸烟者和非吸烟者在两个疗程中完成了实验，在这两个疗程中，使用双盲、平衡对照设计，给他们服用安慰剂或 50mg 的纳曲酮。在休息吸收期、暴露于两种有害刺激（冷压和热痛）后以及在延长的恢复期，采集血液样本和情绪测量数据。阿片类药物阻断增加了催乳素反应，表明内源性阿片类物质系统对催乳素具有抑制作用，这可能是多巴胺对这种激素的刺激作用减弱所致。与不吸烟者相比，吸烟者的反应减弱。催乳素反应也存在性别差异，无论吸烟状况如何，女性对内源性阿片类物质的反应都比男性更强。阿片类药物阻断作用的减弱可能反映了阿片类物质和多巴胺作用的失调。研究结果扩展了先前的报告，表明依赖吸烟者的 HPA 反应的阿片类物质调节作用减弱。
