Striatal Dopamine Release in Response to Ultraviolet Light in Compulsive Tanners

描述（由申请人提供）：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。然而，尽管紫外线辐射引起的疾病和死亡，特别是皮肤癌的比率逐渐增加，但自愿暴露在阳光下的情况仍有增无减。一种越来越普遍的紫外线照射方式是通过室内晒黑沙龙。每年有近3000万美国人，包括20%的18-39岁的人，去室内晒黑沙龙。频繁和过度的晒黑，尽管那些晒黑的人越来越了解与晒黑有关的发病率和死亡率，但这表明紫外线辐射可能会带来超出假设的美容益处的有益效果。事实上，最近的研究表明，高达40%的经常在海滩和沙龙晒黑的人都表现出与成瘾障碍一致的迹象和症状，包括无法减少他们的晒黑频率，强迫性晒黑，和/或尽管有不良后果仍继续晒黑。为了经验性地测量假设的UVR中枢奖励特性，我们使用单光子发射计算机断层扫描（SPECT）评估了市售晒黑床对区域脑血流量（rCBF）的影响，rCBF是脑活动的一种测量方法。强迫性沙龙床晒黑者在两个疗程中被置于UVA/UVB晒黑灯下；一个会话使用活动UVR，另一个会话使用过滤UVR（假UVR）。与假UVR相比，在活动UVR期间，受试者表现出对Tan的渴望显著降低，背纹状体（包括尾状核和壳核）、前叶岛和内侧眶额皮质的rCBF相对增加。这些初步发现表明，紫外线辐射可能具有鼓励过度晒黑的集中奖励特性。由于中纹状体多巴胺能通路在奖励和成瘾中起着关键作用，我们建议通过使用123I-IBZM来扩展这些新发现，以确定是否1)多巴胺在UVR期间释放（正如在对其他奖励的反应中观察到的那样），2)与不经常晒黑的人相比，强迫晒黑者的基底D2/D3受体较低（这一发现在其他成瘾疾病中普遍观察到），以及3)相对于假性UVR，多巴胺外溢是否在UVR反应中，相对于假性UVR，强迫晒黑和不经常晒黑是不同的。如果我们的假设被证明是正确的，这些发现将支持皮肤病-中脉纹体奖励途径，确认强迫性晒黑行为的神经生物学、基于奖励的机制，证明与其他成瘾障碍相似的潜在生物学特征（支持强迫性晒黑者的“成瘾”诊断），为未来研究皮肤病-中脉纹体途径提供框架。并为强迫性晒黑的药物治疗提供理论依据。R21机制获得的数据也将为前瞻性研究提供信息，以证明在本初步研究中未达到显著性的假设比较之间的统计显著性所需的力量。

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.