BACKGROUND: Cocaine Use Disorder (CUD) remains a significant problem in the United States, with high rates of relapse and no present FDA-approved treatment. The acetylcholine neurotransmitter system, specifically through modulation of muscarinic acetylcholine receptor (mAChR) function, has shown promise as a therapeutic target for multiple aspects of CUD. Enhancement of the M OBJECTIVES: To evaluate the effects of cocaine self-administration on M METHODS: Sprague-Dawley rats self-administered cocaine or sucrose pellets for 15 days under 2-h or 4-h sessions followed by PET imaging with [ RESULTS: Cumulative cocaine intake ranged between 324 and 776 mg/kg. Cocaine self-administration was associated with significantly lower [ CONCLUSIONS: These results suggest that cocaine self-administration decreases M