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Light exerts a major influence on human behaviour and health, mainly owing to the importance of sight in our lives, but also due to its entrainment of daily rhythms via the suprachiasmatic nucleus, the master pacemaker. Light may also be a useful clinical medium, as in lumino-therapy for the improvement of depressed mood. Further, as discussed herein, local application of near infrared light to the substantia nigra exerts neuroprotective properties in models of Parkinson's disease. However, light also has a darker side. In general, as regards the growing problem to human health - and the natural world - of excess exposure to artificial light: both urban glow and ubiquitous screens. Moreover, over-exposure to light, in particular fluorescent light, disrupts circadian rhythms and sleep, and may damage dopaminergic neurons. Is it, then, a neglected risk factor for Parkinson's disease? The present article discusses epidemiological and experimental evidence supporting beneficial and potentially deleterious impact of light on dopaminergic neurons and highlights the mechanisms whereby light might influence neuronal tissue., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Recently, employing radioligand displacement and functional coupling studies, we demonstrated that SB269,652 (N-[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide) interacts in an atypical manner with dopamine D 3 receptor displaying a unique profile reminiscent of a negative allosteric ligand. Here, we characterized the binding of radiolabelled [ 3 H]SB269,652 to human dopamine D 3 receptor stably expressed in Chinese Hamster Ovary cells. Under saturating conditions, SB269,652 showed a KD value of ≈ 1nM. Consistent with high selectivity for human dopamine D 3 receptor, [ 3 H]SB269,652 binding was undetectable in cells expressing human dopamine D 1 , D 2L or D 4 receptors and absent in synaptosomes from dopamine D 3 receptor knockout vs. wild-type mice. In contrast to saturation binding experiments, the dissociation kinetics of [ 3 H]SB269,652 from human dopamine D 3 receptors initiated with an excess of unlabelled ligand were best fitted by a bi-exponential binding model. Supporting the kinetic data, competition experiments with haloperidol, S33084 (a dopamine D 3 receptor antagonist) or dopamine, were best described by a two-site model. In co-transfection experiments binding of SB269,652 to dopamine D 3 receptor was able to influence the functional coupling of dopamine D 2 receptor, supporting the notion that SB269,652 is a negative allosteric modulator across receptor dimers. However, because SB269,652 decreases the rate of [ 3 H]nemonapride dissociation, the present data suggest that SB269,652 behaves as a bitopic antagonist at unoccupied dopamine D 3 receptor, binding simultaneously to both orthosteric and allosteric sites, and as a pure negative allosteric modulator when receptors are occupied and it can solely bind to the allosteric site., (Copyright © 2017 Elsevier B.V. All rights reserved.)