This project will develop robust screening methods, new chemical species, and computational screening approaches to target unique heteromeric receptor complexes in the brain that provide rewarding responses to abused drugs. Selectively targeting these CNS-expressed complexes, rather than targeting all receptors in the body, may decrease side effects related to feeding, metabolic function, and cardiovascular health. Validation of this new target approach may be especially important for treatment of stimulant use disorders, where concerns about heart health and eating disorders may otherwise limit the success of therapeutic approaches targeting homomeric or monomeric targets.