Striatal Dopamine Release in Response to Ultraviolet Light in Compulsive Tanners

强迫性晒黑者对紫外线的反应中纹状体多巴胺的释放

• 批准号: 8519310
• 负责人: BRYON H. ADINOFF
• 金额: $ 16.99万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8519310
• 关键词: 123I-IBZM; Alcohols; American; Anterior; Beds; Behavior; Binding; Biologic Characteristic; Biological; Brain; Brain region; Carcinogens; Cerebrovascular Circulation; Cessation of life; Clinical; Cocaine; Corpus striatum structure; Cosmetics; Data; Dermatologic; Development; Diagnosis; Dopamine; Dorsal; Emission-Computed Tomography; Environment; Exhibits; Exploratory/Developmental Grant; Exposure to; Frequencies; Future; Gender; General Population; Genes; Genetic Polymorphism; Goals; Heating; Human; Incidence; Insula of Reil; Intervention; Life; Light; Malignant Neoplasms; Measures; Medial; Mental disorders; Monitor; Morbidity - disease rate; Neuraxis; Neurobiology; Nicotine; Obesity; Opioid; Pathway interactions; Pharmacological Treatment; Photons; Play; Population; Property; Prospective Studies; Radiation-Induced Change; Recording of previous events; Relative (related person); Reporting; Rewards; Sample Size; Severities; Signs and Symptoms; Skin; Skin Cancer; Skin Carcinoma; Skin tanning; Sun Exposure; Sunburn; Sunlight; Synaptic Receptors; System; Testing; UV Radiation Exposure; Ultraviolet B Radiation; Ultraviolet Rays; United Nations; United States Dept. of Health and Human Services; Visit; World Health Organization; addiction; adverse outcome; age group; base; craving; experience; insight; melanoma; mortality; novel; programs; public health relevance; putamen; receptor; receptor density; relating to nervous system; response; sex; single photon emission computed tomography

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.

描述（由申请人提供）：紫外线辐射最近已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 (UVR) 引起的疾病和死亡（尤其是皮肤癌）的发生率逐渐增加，但自愿接触阳光的情况仍然有增无减。越来越常见的 UVR 管理方式是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，其中包括 20% 的 18-39 岁人群。尽管晒黑者越来越了解与晒黑相关的发病率和死亡率，但频繁和过度的晒黑表明，紫外线可能会带来超出假定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表现出与成瘾性疾病一致的体征和症状，包括无法减少晒黑频率、强迫性晒黑和/或不顾不良后果继续晒黑。为了凭经验测量 UVR 假定的中枢有益特性，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 (rCBF) 的影响，rCBF 是大脑活动的测量指标。强迫性沙龙床上晒黑者在两次疗程中被置于 UVA/UVB 晒黑灯下；一次使用主动 UVR，另一次使用过滤 UVR（假 UVR）。在主动 UVR 疗程期间，相对于假 UVR 疗程，受试者表现出对晒黑的渴望显着降低，而背侧纹状体（包括尾状核和壳核）、前岛叶和内侧眶额皮质的 rCBF 相对增加。这些初步研究结果表明，紫外线可能具有促进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发挥着关键作用，我们建议通过使用 123I-IBZM 来扩展这些新发现，以确定 1) UVR 期间是否释放多巴胺（如对其他奖励的反应所观察到的），2) 基础相对于不经常晒黑的人，强迫性晒黑者的 D2/D3 受体较低（在其他成瘾性疾病中常见的发现），以及 3) 是否相对于假 UVR，对 UVR 反应的多巴胺流出在强迫性晒黑者和不经常晒黑者之间有所不同。如果我们的假设被证明是正确的，这些发现将支持皮肤病学-中纹状体奖励通路，确认强迫性晒黑行为的基于奖励的神经生物学机制，证明与其他成瘾性疾病类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-中纹状体通路提供了一个框架，并为开发强迫性晒黑的药物治疗提供了理论基础。 R21 机制获得的数据还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着性的假设比较之间的统计显着性。