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.

Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals / C. Matera, P. Calvé, V. Casadó-Anguera, R. Sortino, A.M.J. Gomila, E. Moreno, T. Gener, C. Delgado-Sallent, P. Nebot, D. Costazza, S. Conde-Berriozabal, M. Masana, J. Hernando, V. Casadó, M.V. Puig, P. Gorostiza. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 23:17(2022 Sep 04), pp. 10114.1-10114.18. [10.3390/ijms231710114]

Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals

C. Matera
Primo
;
2022-09-04

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 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.
GPCR; azobenzene; behavior; brainwave; dopamine; in vivo electrophysiology; optogenetics; optopharmacology; photochromism; photopharmacology; photoswitch; zebrafish;
Settore CHIM/08 - Chimica Farmaceutica
Settore CHIM/06 - Chimica Organica
Settore BIO/14 - Farmacologia
https://www.mdpi.com/1422-0067/23/17/10114
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/937547
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