Drug addiction is a pernicious and prevalent problem with little available for clinical treatment. This presentation will review the presenter's recent studies that show roles for the ventral pallidum (VP), ventral tegmental area (VTA) dopamine (DA), and orexin/hypocretin brain systems in cocaine seeking and demand. A within-session behavioral economic paradigm revealed potent contributions of the VTA DA system to demand for cocaine. The presenter used designer receptors exclusively activated by designer drugs (DREADDs) to show that the projection from VP to VTA DA neurons is critical for cocaine seeking. Additional pharmacologic studies reveal that orexin inputs to VTA interact with glutamate inputs and those from VP to augment cocaine seeking elicited by cocaine-associated cues. The presentation concludes that DREADDs are a promising avenue for novel therapies to treat drug abuse.