While prescription opioid analgesics are effective for treating nociceptive and inflammatory pain, long-term use of these medications may lead to opioid use disorders and in some cases fatal overdose. As it stands, drug overdoses are the leading cause of injury-related deaths in the United States. Despite efficacious medications to treat opioid use disorder, there is still a high rate of relapse following detoxification. Thus, there is a critical need for research aimed at identifying novel pharmacotherapies to treat opioid use disorder including adjunct medications that augment opioid-induced analgesia and reduce the abuse liability of these drugs. A growing body of literature indicates that glucagon-like peptide-1 (GLP-1) receptor agonists reduce drug reinforcement in animal models. Recent studies from our lab demonstrate that systemic administration of the GLP-1R agonist exendin-4 into the nucleus accumbens (NAc) attenuates oxycodone taking and the reinstatement of oxycodone seeking behaviors in rats. We further identified behaviorally relevant doses of exendin-4 which did not produce adverse feeding effects in opioid-dependent rats. We then characterized GLP-1R-expressing neurons in the NAc to identify striatal microcircuits underlying the effects of exendin-4 on drug taking. The NAc is composed of GABAergic medium spiny neurons (MSNs) primarily expressing D1-like or D2-like dopamine receptors, cholinergic interneurons, and GABAergic interneurons. Using fluorescent in situ hybridization, we labeled GLP-1 receptor, dopamine D1 receptor (D1R), and dopamine D2 receptor (D2R) transcripts in the NAc. Additionally, we labeled choline acetyltransferase (ChAT), a marker for cholinergic interneurons, and glial fibrillary acidic protein (GFAP), a marker for astrocytes. Our preliminary findings show that GLP-1 receptors are expressed on D1R-MSNs and D2R-MSNs as well as on cholinergic interneurons and astrocytes in the NAc.  Previous studies showed that cholinergic interneurons in the NAc modulate motivated behaviors by regulating striatal dopamine release. Since GLP-1 receptors are expressed on cholinergic interneurons in the NAc, we hypothesize that activation of NAc GLP-1 receptors attenuates oxycodone taking and seeking behaviors by stimulating NAc cholinergic interneurons. Future experiments will therefore examine whether GLP-1R knockdown in NAc cholinergic interneurons blocks the suppressive effects of GLP-1R agonists on opioid taking and seeking. Together, these findings suggest that GLP-1 receptors may potentially serve as molecular targets to reduce opioid abuse liability.