Validating a novel chemogenetic strategy for opioid use disorder

Project Summary Opioid use disorder (OUD) is a debilitating condition that represents a significant public health burden. Current treatments are ineffective for many patients because they require lifelong adherence to a strict medication regimen to be effective. Thus, there is an urgent need to develop new treatments for OUD in which a single treatment can confer long-lasting protection. Here we propose to test an innovative new chemogenetic strategy to achieve this by suppressing opioid-induced dopamine release in the nucleus accumbens, one of the main mechanisms underlying OUD. In Aim 1, we test whether using adeno-associated viral vectors to express a novel chemogenetic receptor in the brain can suppress opioid-induced dopamine release. In Aim 2, we will test whether this approach can selectively reduce opioid consumption without affecting other behaviors. In Aim 3, we will test whether this approach can extinguish opioid consumption in animals with a previous history of opioid self-administration. We anticipate that this study will provide the proof-of-concept necessary to continue with further refinement of this technology, with the long-term goal of developing a one-time treatment that can confer lifelong protection against OUD.