Striatal Dopamine Release in Response to Ultraviolet Light in Compulsive Tanners

描述（由申请人提供）：美国卫生与公众服务部最近将紫外线辐射归类为已知的人类致癌物。然而，尽管紫外线辐射（UVR）引起的疾病和死亡，特别是皮肤癌的发生率逐渐增加，但自愿暴露在阳光下的情况仍然有增无减。一种越来越常见的紫外线管理形式是通过使用室内晒黑沙龙。每年有近3000万美国人，包括20%的18-39奥尔兹的年轻人，参观室内日光浴沙龙。频繁和过度的晒黑，尽管越来越多的人了解与晒黑相关的发病率和死亡率，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%的频繁海滩和沙龙晒日光浴者表现出与成瘾性疾病一致的体征和症状，包括无法减少晒日光浴频率，强迫性晒日光浴和/或尽管有不良后果仍继续晒日光浴。为了经验性地测量UVR的假定中枢奖励特性，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局部脑血流量（rCBF）的影响，rCBF是大脑活动的一种测量方法。强迫沙龙床tablets被放置在UVA/UVB晒黑灯在两个会议期间;一个会议与积极的UVR和过滤的UVR（假UVR）。在主动UVR会话期间，相对于假UVR会话，受试者表现出对晒黑的渴望显著降低，背侧纹状体（包括尾状核和壳核）、前额叶和内侧眶额皮质的rCBF相对增加。这些初步研究结果表明，紫外线可能具有中央奖励性质，鼓励过度晒黑。由于中纹状体多巴胺能通路在奖赏和成瘾中起着关键作用，我们建议通过使用123 I-IBZM来确定1）多巴胺在UVR期间是否释放，以扩展这些新发现（正如在对其他奖励的反应中所观察到的那样），2）相对于不频繁的抽搐，强迫性抽搐中的基础D2/D3受体较低（在其他成瘾性疾病中常见的发现），和3）是否多巴胺流出响应UVR，相对于假UVR，在强迫性和罕见的癫痫之间有所不同。如果我们的假设被证明是正确的，这些发现将支持皮肤-中纹状体奖励通路，证实强迫性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相似的潜在生物学特征。（支持强迫性癫痫的“成瘾”诊断），为未来的研究提供了一个框架，以检查皮肤-中纹状体通路，并为开发用于强迫性晒黑的药物治疗提供了理论基础。通过R21机制获得的数据还将为前瞻性研究提供关于证明本初步研究中未达到显著性的假设比较之间的统计学显著性所需的把握度的信息。 公共卫生相关性：尽管紫外线辐射引起的疾病和死亡，特别是皮肤癌的发病率逐渐增加，但日光浴床的暴露仍然有增无减。尽管普通人群（以及晒黑的人）对其相关的发病率和死亡率的了解越来越多，但频繁和过度的晒黑表明，来自阳光和晒黑床的紫外线辐射可能会带来超出假设的美容益处的有益效果。了解过度晒黑所涉及的中枢神经系统奖励机制将为减少过度晒黑的治疗干预提供目标。

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. PUBLIC HEALTH RELEVANCE: Exposure to tanning beds continues unabated despite progressively increasing rates of ultraviolet radiation- induced illness and death, particularly skn cancer. Frequent and excessive tanning, in spite of a growing understanding by the general population (as well as by those who tan) of its associated morbidity and mortality, suggests that the ultraviolet radiation from sunlight and tanning beds may impart rewarding effects beyond the assumed cosmetic benefits. An understanding of the central nervous system reward mechanisms involved in excessive tanning will provide targets for treatment interventions to decrease excessive tanning.