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Title: Reversible photocontrol of dopaminergic transmission in wild-type animals
Author: Matera, Carlo
Calvé, Pablo
Casadó Anguera, Verònica
Sortino, Rosalba
Gomila, Alexandre M.J.
Moreno Guillén, Estefanía
Gener, Thomas
Delgado-Sallent, Cristina
Nebot, Pau
Costazza, Davide
Conde-Berriozabal, Sara
Masana Nadal, Mercè
Hernando, Jordi
Casadó, Vicent
Puig, M.Victoria
Gorostiza Langa, Pablo Ignacio
Keywords: Dopamina
Issue Date: 4-Sep-2022
Publisher: MDPI
Abstract: 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 time scale 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 illuminationdependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wildtype animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes.
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It is part of: International Journal of Molecular Sciences, 2022, vol. 23, num. 10114, p. 1-18
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ISSN: 1661-6596
Appears in Collections:Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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