Cholinergic and dopaminergic-mediated motivated behavior in healthy states and in substance use and mood disorders.

Acetylcholine is an important neuromodulator of the mesolimbic dopamine (DA) system, which itself is a mediator of motivated behavior. Motivated behavior can be described by two primary components, termed directional and activational motivation, both of which can be examined and dissociated using effort-choice tasks. The directional component refers to motivated behavior directed towards reinforcing stimuli and away from aversive stimuli. Behaviors characterized by increased vigor, persistence, and work output are considered to reflect activational components of motivation. Disruption of DA signaling has been shown to decrease activational components of motivation, while leaving directional features intact. Facilitation of DA release promotes the activational aspects of motivated behavior. In this review, we discuss cholinergic and DA regulation of motivated behaviors. We place emphasis on effort-choice processes and the ability of effort-choice tasks to examine and dissociate changes of motivated behavior in the context of substance use and mood disorders. Furthermore, we consider how altered cholinergic transmission impacts motivated behavior across disease states, and the possible role of cholinergic dysregulation in the etiology of these illnesses. Finally, we suggest that treatments targeting cholinergic activity may be useful in ameliorating motivational disruptions associated with substance use and comorbid substance use and mood disorders.