Identifying the precise location of cholinergic effects on psychostimulant reward has been difficult because systemic administration of drugs and genetic deletion models affect receptors throughout the nervous system. However, recent work has focused attention on the NAc as a site of interaction between cholinergic mechanisms and cocaine reinforcement [39]. ACh interneurons in the NAc are known to be responsive to cocaine self-administration [40,41]. Hikida et al (2001) reported that selective ablation of cholinergic interneurons within the NAc using immunotoxin-mediated cell targeting resulted in increased cocaine-induced locomotor activity and reward value (as measured by conditioned place preference). In contrast, augmentation of ACh levels with acetylcholinesterase inhibitors in lesioned mice had the opposite effect [42,43]. These studies provide strong evidence that cholinergic cells in the NAc play an important role in modulating the reinforcing value of psychostimulants, but the nature of the cholinergic receptors that are critical for this effect remains unclear.
