Striatal Dopamine Release in Response to Ultraviolet Light in Compulsive Tanners

描述(申请人提供)：紫外线辐射最近被美国卫生与公众服务部列为已知的人类致癌物质。然而，尽管紫外线辐射(UVR)导致的疾病和死亡，特别是皮肤癌的发病率逐渐上升，但自愿暴露在阳光下的情况仍未减弱。一种越来越常见的UVR管理形式是通过使用室内日光浴沙龙。每年有近3000万美国人光顾室内日光浴沙龙，其中20%的人年龄在18-39岁之间。频繁和过度的晒黑，尽管那些晒黑的人越来越了解与晒黑相关的发病率和死亡率，但这表明UVR可能会带来比假定的美容好处更有价值的效果。事实上，最近的研究表明，高达40%的海滩和沙龙经常晒黑的人都表现出与成瘾性障碍一致的体征和症状，包括无法减少晒黑频率，强迫晒黑，和/或不顾不良后果继续晒黑。为了经验性地测量UVR假定的中枢回报特性，我们使用单光子发射计算机断层扫描(SPECT)评估了商用日光浴床对局部脑血流量(RCBF)的影响，rCBF是衡量大脑活动的指标。在两个疗程中，强迫症沙龙床上的皮肤被置于UVA/UVB日光灯下；一次是活动紫外线照射，另一次是过滤紫外线照射(假紫外线照射)。在活跃的UVR训练中，与假UVR训练相比，受试者对TAN的欲望显著降低，而背侧纹状体(包括尾状核和壳核)、前岛和内侧眶前叶皮质的rCBF相对增加。这些初步发现表明，UVR可能具有鼓励过度晒黑的中央奖励特性。由于中纹状体多巴胺能通路在奖赏和成瘾中起关键作用，我们建议通过使用123I-IBZM来扩展这些新的发现，以确定1)在UVR期间是否释放多巴胺(正如在对其他奖赏的反应中观察到的那样)，2)基础D2/D3受体在强迫症患者中比不频繁的患者低(这一发现在其他成瘾障碍中通常被观察到)，以及3)相对于假的UVR，强迫症患者和不频繁的患者之间是否存在不同的多巴胺外流。如果我们的假设被证明是正确的，这些发现将支持皮肤学-中纹状体的奖赏途径，证实强制晒黑行为的神经生物学、基于奖励的机制，展示与其他成瘾性疾病类似的潜在生物学特征(支持对强迫性晒黑的“成瘾”诊断)，为未来研究检查皮肤学-中纹状体途径提供框架，并为开发强迫性晒黑的药物治疗提供理论基础。R21机制获得的数据也将为前瞻性研究提供必要的力量，以证明在这项初步研究中未达到显著意义的假设性比较之间的统计学意义。

DESCRIPTION (provided by applicant): UV radiation has recently been classified as a known human carcinogen by the US Department of Health and Human Services. Nevertheless, the voluntary exposure to sunlight continues unabated despite progressively increasing rates of ultraviolet radiation (UVR)-induced illness and death, particularly skin cancer. An increasingly common form of UVR administration is through the use of indoor tanning salons. Almost 30 million Americans, including 20% of 18-39 year olds, visit indoor tanning salons each year. Frequent and excessive tanning, despite a growing understanding by those who tan of the morbidity and mortality associated with tanning, suggests that UVR may impart rewarding effects beyond the assumed cosmetic benefits. Recent studies, in fact, have shown that up to 40% of both frequent beach and salon tanners exhibit signs and symptoms consistent with an addictive disorder, including an inability to decrease their tanning frequencies, compulsive tanning, and/or continued tanning despite adverse consequences. To empirically measure putative centrally rewarding properties of UVR, we assessed the effects of a commercially available tanning bed upon regional cerebral blood flow (rCBF), a measure of brain activity, using single-photon emission computed tomography (SPECT). Compulsive salon bed tanners were placed under a UVA/UVB tanning light during two sessions; one session with active UVR and the other with filtered UVR (sham UVR). During the active UVR session, relative to sham UVR session, subjects demonstrated both a significant decrease in Desire to Tan and a relative increase in rCBF of the dorsal striatum (including caudate and putamen), anterior insula, and medial orbitofrontal cortex. These preliminary findings suggest that UVR may have centrally rewarding properties that encourage excessive tanning. As the mesostriatal dopaminergic pathway plays a key role in reward and addiction, we propose to extend these novel findings by using 123I-IBZM to determine if 1) dopamine is released during UVR (as is observed in response to other rewards), 2) basal D2/D3 receptors are lower in compulsive tanners relative to infrequent tanners (a finding commonly observed in other addictive disorders), and 3) whether dopamine efflux in response to UVR, relative to sham UVR, differs between compulsive and infrequent tanners. If our hypotheses are proven correct, these findings will support a dermatologic-mesostriatal reward pathway, confirm a neurobiological, reward-based mechanism for compulsive tanning behaviors, demonstrate underlying biological characteristics similar to other addictive disorders (supporting an "addiction" diagnosis for compulsive tanners), offer a framework for future studies to examine dermatologic-mesostriatal pathways, and provide a rationale for the development of pharmacological treatments for compulsive tanning. Data obtained by the R21 mechanism will also inform prospective studies regarding the power necessary to demonstrate statistical significance between hypothesized comparisons not reaching significance in this preliminary study.