Optopharmacology and Sensors for Dissecting Opioid Action In Vivo

PROJECT SUMMARY
In 2019, abuse of prescription and illicit opioids resulted in an estimated over 47,000 deaths in the United States.
The transition from therapeutic use to destructive opioid use disorder occurs through the maladaptive activation
of mesocorticolimbic circuits. Despite decades of research linking these pathways with opioids, surprisingly little
is understood about how opioids modulate the brain in vivo in space and time in freely moving animals. This is,
in part, driven by the inability to detect and monitor opioids at sub-second timescales. Together, these
issues highlight the need for significant advancements for “in vivo precision pharmacology” as indicated
specifically in this RFA-DA-20-019 NIDA program announcement. Recent developments using
photoactivatable opioid compounds (optopharmacology) together with new optofluidic hardware devices show
exciting promise for finally understanding the temporal characteristics of opioid signaling. However, further
advances in opioid detection and activation are necessary for fully decoding how opioids modulate neural circuits
in vivo. Here we address this challenge head on with a multi-disciplinary team of biochemists, neuroscientists
and bioengineers. We will utilize a series of cutting-edge approaches to: 1) develop novel opioid sensors for in
vivo, sub-second measures of fentanyl, morphine, and methadone, 2) demonstrate the utility of
optopharmacological approaches for dissecting opioid action, and 3) apply the sensors and optopharmacological
approaches to perform in vivo precision pharmacological experiments to modulate pain and reward circuits
related to drug abuse.

Grant Number: 5R33DA051489-05
NIH Institute/Center: NIH
Principal Investigator: Michael Bruchas