Photouncaging of an Opioid Peptide in Vivo Using Blue Light

Here we report blue light-driven in vivo photoactivation of TCA-DCCM-DAMGO, a caged derivative of the μ-opioid receptor (MOR) agonist DAMGO. TCA-DCCM-DAMGO is chemically stable in the dark, is inactive prior to illumination, and cleanly liberates DAMGO upon irradiation with blue light. Brain slice electrophysiology demonstrates rapid, light-triggered MOR activation. Following intracerebroventricular infusion of TCA-DCCM-DAMGO in the mouse brain, photoactivation in the ventral tegmental area with blue light elicited a rapid, opioid-dependent increase in locomotion. These results demonstrate the feasibility of in vivo photouncaging using blue light deep in the mouse brain and establish TCA-DCCM-DAMGO as a probe for manipulating endogenous opioid receptors in behaving animals.