Sign- versus goal trackers, top down control of attention, and underlying cholinergic mechanisms

The propensity to attribute incentive salience to reward cues has been hypothesized to indicate vulnerability for addiction-like behavior. Evidence in support of this hypothesis has been obtained from experiments studying animals which, using a Pavlovian conditioned approach test, were categorized as ‘sign-trackers’ (ST). In contrast to ST, ‘goal-trackers’ (GT) do not readily attribute incentive salience to reward cues and are less vulnerable for developing addiction-like behavior. Our research is guided by the hypothesis that ST, when compared with GT, exhibit lower levels of cognitive control of attention, thereby fostering behaviors that interfere with (sustained) attentional performance. Furthermore, as cholinergic modulation of prefrontal circuitry serves as a top-down signal for attention, we hypothesized that attentional performance-associated increases in prefrontal cholinergic neurotransmission are lower in ST than GT. ST and GT were trained and extensively practiced the Sustained Attention Task (SAT). This task consists of signal and non-signal trials and animals are rewarded for hits and correct rejections, respectively, while misses and false alarms trigger the inter-trial interval but have no further scheduled consequences. Asymptotic SAT performance of ST was characterized by lower hit rates when compared with GT. ST more frequently disengaged from orienting toward the intelligence panel, thereby missing signals. Because non-signal trial responding appears to represent the default response mode for all animals, limitations in the ability to sustain attention toward the signal source did not result in lower rates of correct rejections. SAT-associated increases in cholinergic neurotransmission, assessed by using microdialysis, were significantly lower in ST. Because this tonic component of cholinergic neurotransmission modulates prefrontal circuitry via alpha4beta2* nicotinic acetylcholine receptors (nAChRs), we also tested the hypothesis that blocking these receptors in GT disrupts SAT performance. Systemic administration of the relatively beta2*-selective nAChR antagonist dihydro-beta-erythroidine (5.0 mg/kg; i.p.) selectively reduced the hit rate in GT. Collectively, these findings indicate a limited capacity of ST to sustain attention and suppress competing behaviors. This is a key cognitive trait in individuals vulnerable for addiction, in part because it rapidly exhausts the capacity for filtering drug cues and for attending to alternative task cues and engaging in alternative behavior.