“Non-image-forming” (NIF) effects of light are mediated primarily by a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment, melanopsin (OPN4). These NIF functions include circadian entrainment, pupillary reflexes, and photic effects on sleep, mood, and cognition. We recently reported that mice of multiple genotypes exhibit reduced voluntary ethanol intake under both constant darkness (DD) and constant light (LL) relative to standard light-dark (LD) conditions. In the present study, we sought to determine whether these effects are mediated by melanopsin-expressing ipRGCs and their potential relationship to photic effects on the circadian system. To this end, we examined the effects of environmental lighting regimen on both ethanol intake and circadian activity rhythms in a genetically engineered mouse model (Opn4^aDTA/aDTA) in which melanopsin expression is completely blocked while ipRGCs are progressively ablated due to activation of attenuated diphtheria toxin A (aDTA) transgene under the control of the Opn4 promoter. As expected from previous studies, Opn4^aDTA/aDTA mice displayed dramatic attenuation of circadian photosensitivity, but surprisingly, showed identical suppression of ethanol intake under both DD and LL as that seen in controls. These results demonstrate that the effects of lighting regimen on voluntary ethanol intake are independent of melanopsin-expressing ipRGCs and ipRGC-mediated photic effects on the circadian system. Rather, these effects are likely mediated by classical retinal photoreceptors and central pathways.

光的“非图像形成”(NIF) 效应主要由表达光色素黑视素 (OPN4) 的固有光敏视网膜神经节细胞 (ipRGC) 的子集介导。这些 NIF 功能包括昼夜节律调节、瞳孔反射以及对睡眠、情绪和认知的光效应。我们最近报道，相对于标准明暗 (LD) 条件，在恒定黑暗 (DD) 和恒定光照 (LL) 下，多种基因型的小鼠表现出的自愿乙醇摄入量减少。在本研究中，我们试图确定这些影响是否由表达黑视素的 ipRGC 介导，以及它们与光对昼夜节律系统的影响的潜在关系。为此，Opn4 ^aDTA/aDTA )，其中由于在Opn4启动子控制下的减毒白喉毒素 A (aDTA) 转基因的激活，黑视蛋白表达被完全阻断，而 ipRGCs 逐渐消融。正如先前研究所预期的那样，Opn4 ^aDTA/aDTA小鼠显示出昼夜节律光敏性的显着减弱，但令人惊讶的是，在 DD 和 LL 下显示出与对照组相同的乙醇摄入抑制。这些结果表明，光照方案对自愿乙醇摄入的影响与表达黑视蛋白的 ipRGC 和 ipRGC 介导的光对昼夜节律系统的影响无关。相反，这些效应可能是由经典的视网膜光感受器和中枢通路介导的。