Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals

Carlo Matera, Pablo Calvé, Verònica Casadó-Anguera, Rosalba Sortino, Alexandre M.J. Gomila, Estefanía Moreno, Thomas Gener, Cristina Delgado-Sallent, Pau Nebot, Davide Costazza, Sara Conde-Berriozabal, Mercè Masana, Jordi Hernando, Vicent Casadó, M. Victoria Puig, Pau Gorostiza*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Article number10114
Number of pages18
JournalInternational journal of molecular sciences
Issue number17
Publication statusPublished - Sept 2022


  • GPCR
  • azobenzene
  • behavior
  • brainwave
  • dopamine
  • in vivo electrophysiology
  • optogenetics
  • optopharmacology
  • photochromism
  • photopharmacology
  • photoswitch
  • zebrafish


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