Beyond dopamine: Broader neuromodulatory contributions in sign- and goal-tracking

Sign- and goal-tracking behaviors provide a powerful framework for understanding individual differences in cue-motivated responding and vulnerability to addiction. While dopamine has long been recognized as central to the attribution of incentive salience, growing evidence indicates that multiple neuromodulatory systems contribute to these behaviors through distinct mechanisms. This review synthesizes findings on the cholinergic, serotonergic, adrenergic, opioid, and stimulant (nicotine, caffeine) systems in modulating sign- and goal-tracking in rodents. A better understanding of these mechanisms may guide individualized interventions to reduce cue-triggered relapse and improve addiction treatment outcomes.