Moulin Thiago C, Ferro Federico, Berkins Samuel, Hoyer Angela, Williams Michael J, Schiöth Helgi B
Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, 751 24 Uppsala, Sweden.
Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, 119146 Moscow, Russia.
Brain Sci. 2020 Jul 28;10(8):487. doi: 10.3390/brainsci10080487.
Imbalances in dopaminergic signaling during development have been indicated as part of the underlying neurobiology of several psychiatric illnesses, including schizophrenia, major depression, bipolar disorder, and food addiction. Yet, how transient manipulation of dopaminergic signaling influences long-lasting behavioral consequences, or if these modifications can induce inheritable traits, it is still not understood. In this study, we used the model to test if transient pharmacological activation of the dopaminergic system leads to modulations of feeding and locomotion in adult flies. We observed that transient administration of a dopaminergic precursor, levodopa, at 6 h, 3 days or 5 days post-eclosion, induced overfeeding behavior, while we did not find significant effects on locomotion. Moreover, this phenotype was inherited by the offspring of flies treated 6 h or 3 days post-eclosion, but not the offspring of those treated 5 days post-eclosion. These results indicate that transient alterations in dopaminergic signaling can produce behavioral alterations in adults, which can then be carried to descendants. These findings provide novel insights into the conditions in which environmental factors can produce transgenerational eating disorders.
发育过程中多巴胺能信号的失衡已被指出是包括精神分裂症、重度抑郁症、双相情感障碍和食物成瘾在内的几种精神疾病潜在神经生物学的一部分。然而,多巴胺能信号的短暂操纵如何影响长期行为后果,或者这些改变是否能诱导可遗传特征,目前仍不清楚。在本研究中,我们使用该模型来测试多巴胺能系统的短暂药理学激活是否会导致成年果蝇的进食和运动调节。我们观察到,在羽化后6小时、3天或5天短暂给予多巴胺能前体左旋多巴会诱导过度进食行为,而我们未发现对运动有显著影响。此外,这种表型在羽化后6小时或3天接受处理的果蝇后代中得以遗传,但在羽化后5天接受处理的果蝇后代中未出现。这些结果表明,多巴胺能信号的短暂改变可在成体中产生行为改变,进而传递给后代。这些发现为环境因素可导致跨代饮食失调的情况提供了新的见解。