Abstract：
Substance use disorder (SUD) affects over 48 million Americans aged 12 and over. Thus, identifying novel chemicals contributing to SUD will be critical for developing efficient prevention and mitigation strategies. Considering the complexity of the actions and effects of these substances on human behavior, a high-throughput platform using a living organism is ideal. We developed a quick and easy screening assay using Caenorhabditis elegans. C. elegans prefers high-quality food (Escherichia coli HB101) over low-quality food (Bacillus megaterium), with a food preference index of approximately 0.2, defined as the difference in the number of worms at E. coli HB101 and B. megaterium over the total worm number. The food preference index was significantly increased by loperamide, a μ-opioid receptor (MOPR) agonist, and decreased by naloxone, a MOPR antagonist. These changes depended on npr-17, a C. elegans homolog of opioid receptors. In addition, the food preference index was significantly increased by arachidonyl-2\'-chloroethylamide, a cannabinoid 1 receptor (CB1R) agonist, and decreased by rimonabant, a CB1R inverse agonist. These changes depended on npr-19, a homolog of CB1R. These results suggest that the conserved opioid and endocannabinoid systems modulate the food preference behaviors of C. elegans. Finally, the humanoid C. elegans strains where npr-17 was replaced with human MOPR and where npr-19 was replaced with human CB1R phenocopied the changes in food preference by the drug treatment. Together, the current results show that this method can be used to rapidly screen the potential effectors of MOPR and CB1R to yield results highly translatable to humans.
摘要：
物质使用障碍（SUD）影响超过6100万12岁及以上的美国人。因此，确定有助于SUD的新型化学物质对于制定有效的预防和缓解策略至关重要。考虑到这些物质对人类行为的作用和影响的复杂性，使用生物体的高通量平台是理想的。我们使用秀丽隐杆线虫开发了一种快速简便的筛查方法。C.线虫更喜欢高质量的食物（大肠杆菌HB101）而不是低质量的食物（巨大芽孢杆菌），食物偏好指数约为0.2，定义为大肠杆菌HB101和巨大芽孢杆菌的蠕虫数量与总蠕虫数量的差异。洛哌丁胺显著提高了食物偏好指数，μ阿片受体（MOPR）激动剂，并通过纳洛酮减少，MOPR拮抗剂。这些变化取决于npr-17，一种阿片受体的秀丽隐杆线虫同源物。此外,花生四烷基-2'-氯乙基酰胺显著增加了食物偏好指数，大麻素1受体（CB1R）激动剂，被利莫那班减少了，CB1R反向激动剂。这些变化取决于CB1R的同源物npr-19。这些结果表明，保守的阿片样物质和内源性大麻素系统调节秀丽隐杆线虫的食物偏好行为。最后,npr-17被人类MOPR取代，npr-19被人类CB1R取代的人形秀丽隐杆线虫菌株通过药物治疗表现出食物偏好的变化。一起,目前的结果表明，该方法可用于快速筛选MOPR和CB1R的潜在效应物，以产生高度可转化为人类的结果。
