Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals.

Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here, we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a timescale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illumination-dependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes.

Genomics and epigenomics of addiction.

Recent progress in the genomics and epigenomics of addiction has contributed to improving our understanding of this complex mental disorder's etiology, filling the gap between genes, environment, and behavior. We review the behavioral genetic studies reporting gene and environment interactions that explain the polygenetic contribution to the resilience and vulnerability to develop addiction. We discuss the evidence of polymorphic candidate genes that confer susceptibility to develop addiction as well as the studies of specific epigenetic marks that contribute to vulnerability and resilience to addictive-like behavior. A particular emphasis has been devoted to the miRNA changes that are considered potential biomarkers. The increasing knowledge about the technology required to alter miRNA expression may provide promising novel therapeutic tools. Finally, we give future directions for the field's progress in disentangling the connection between genes, environment, and behavior.