Cholinergic control over attention in rats prone to attribute incentive salience to reward cues.

Some rats [sign-trackers (STs)] are especially prone to attribute incentive salience to reward cues, relative to others [goal-trackers (GTs)]. Thus, reward cues are more likely to promote maladaptive reward-seeking behavior in STs than GTs. Here, we asked whether STs and GTs differ on another trait that can contribute to poor restraint over behavior evoked by reward cues. We report that, relative to GTs, STs have poor control over attentional performance, due in part to insufficient cholinergic stimulation of cortical circuitry. We found that, relative to GTs, STs showed poor performance on a sustained attention task (SAT). Furthermore, their performance fluctuated rapidly between periods of good to near-chance performance. This finding was reproduced using a separate cohort of rats. As demonstrated earlier, performance on the SAT was associated with increases in extracellular levels of cortical acetylcholine (ACh); however, SAT performance-associated increases in ACh levels were significantly attenuated in STs relative to GTs. Consistent with the view that the modulatory effects of ACh involve stimulation of α4β2* nicotinic ACh receptors (nAChRs), systemic administration of the partial nAChR agonist ABT-089 improved SAT performance in STs and abolished the difference between SAT-associated ACh levels in STs and GTs. Neither the nonselective nAChR agonist nicotine nor the psychostimulant amphetamine improved SAT performance. These findings suggest that individuals who have a propensity to attribute high-incentive salience to reward cues also exhibit relatively poor attentional control. A combination of these traits may render individuals especially vulnerable to disorders, such as obesity and addiction.