Of the many perspectives Hoebel brought to the study of neurochemical modulation of motivated behavior, perhaps the most salient for this review – and one that inspired much of the work presented herein – has been his view (along with that of Dr. Pedro Rada) that acetylcholine constitutes an integral component of the mesolimbic system [11]. Cholinergic pathways interact with key regions in the brain reward circuit, as illustrated in Figure 1. ACh projections from the nucleus basalis (NB) provide input to cortical and subcortical regions of the hippocampus and amygdala. These projections may play a role in learning and memory processes that are implicated in drug-induced dysfunctions like craving and relapse [12,13]. From the DA cell body region of the ventral tegmental area (VTA), DA terminals synapse on medium spiny gamma-aminobutyric acid (GABA)-containing cells and a smaller population of large, aspiny acetylcholine (ACh) -containing interneurons in the NAc [14]. Cholinergic interneurons have large dendritic arbors and an extensive network of axons that contact many cell bodies and terminals within both the core and shell subdivisions of the NAc [15,16].