The common attributes of the agonists and antagonists affected their attentional performance on the rCET

Paying special consideration to these drugs’ interactions with animals’ existing choice preferences. Here we show for the first time the influence of cholinergic functioning on decision making with attentional effort costs. The nAChR agonist nicotine decreased choice of high-effort/highreward trials for “slacker” rats, despite a modest improvement in these animals’ performance, whereas the drug did not affect workers’ choice. In contrast to its differential choice effects for workers versus slackers, nicotine increased motor impulsivity for all animals. Interestingly, the mAChR antagonist scopolamine also decreased choice of HR, particularly for workers, without any concomitant effects on performance or motor impulsivity. Finally, the mAChR agonist oxotremorine had no effect on choice but dose-dependently decreased impulsive responding. Taken together, these data support recent findings that nicotinic and muscarinic cholinergic systems subserve cost/benefit decision making, and further demonstrate that acetylcholine’s influence on choice can be dissociated from its effects on attentional performance and motor impulsivity. Central acetylcholine largely originates from the basal forebrain and pons, and projects to a diffuse set of targets in the central nervous system, including the prefrontal cortex, limbic Epoxomicin regions, and the midbrain dopaminergic system ; a small population of cholinergic interneurons is also located in the striatum and projects locally, and thus acetylcholine exerts modulatory control over both dopamine’s midbrain source and its striatal targets. Broadly speaking, then, central cholinergic systems are excellently placed to both directly and indirectly contribute to the previously established “cortico-limbic-striatal” circuitry that underlies cost/ benefit decision making. Moreover, these distinct cholinergic pathways, for example to prefrontal cortex versus striatum, may make their own unique contributions to the decision-making process. Pharmacological studies of cholinergic contributions to decision making have primarily used delay- and risk-discounting tasks, wherein the costs of the HR option were adjusted across blocks within each session. On the risk-discounting task, nicotine increased choice of HR when costs ascended across blocks, whereas it decreased choice of HR when costs descended across blocks, indicating that the drug impaired animals’ behavioral flexibility. Scopolamine robustly decreased choice of HR on both tasks. Only null effects on decision making have been reported for mecamylamine and oxotremorine, despite their nonspecific motor effects indicating a physiologically relevant dose range. These parallel the current data and suggest that these drugs may not be ideal for systemic manipulations of cost/benefit decision-making tasks, although they may be useful for injection into specific brain regions. As a comparison, the muscarinic agonist pilocarpine decreased choice.

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