Nicotine Increases Impulsivity and Decreases Willingness to Exert Cognitive Effort despite Improving Attention in “Slacker” Rats: Insights into Cholinergic Regulation of Cost/Benefit Decision Making

Abstract

Successful decision making in our daily lives requires weighing an option’s costs against its associated benefits. The neuromodulator acetylcholine underlies both the etiology and treatment of a number of illnesses in which decision making is perturbed, including Alzheimer’s disease, attention-deficit/hyperactivity disorder, and schizophrenia. Nicotine acts on the cholinergic system and has been touted as a cognitive enhancer by both smokers and some researchers for its attention-boosting effects; however, it is unclear whether treatments that have a beneficial effect on attention would also have a beneficial effect on decision making. Here we utilize the rodent Cognitive Effort Task (rCET), wherein animals can choose to allocate greater visuospatial attention for a greater reward, to examine cholinergic contributions to both attentional performance and choice based on attentional demand. Following the establishment of baseline behavior, four drug challenges were administered: nicotine, mecamylamine, scopolamine, and oxotremorine (saline plus three doses for each). As per previous rCET studies, animals were divided by their baseline preferences, with “worker” rats choosing high-effort/high-reward options more than their “slacker” counterparts. Nicotine caused slackers to choose even fewer high-effort trials than at baseline, but had no effect on workers’ choice. Despite slackers’ decreased willingness to expend effort, nicotine improved their attentional performance on the task. Nicotine also increased measures of motor impulsivity in all animals. In contrast, scopolamine decreased animals’ choice of high-effort trials, especially for workers, while oxotremorine decreased motor impulsivity for all animals. In sum, the cholinergic system appears to contribute to decision making, and in part these contributions can be understood as a function of individual differences. While nicotine has been considered as a cognitive enhancer, these data suggest that its modest benefits to attention may be coupled with impulsiveness and decreased willingness to work hard, especially in individuals who are particularly sensitive to effort costs (i.e. slackers).

Investigating serotonergic contributions to cognitive effort allocation, attention, and impulsive action in female rats

“…We opted to use female rats in the current study, given that they display similar patterns of behaviour on the rCET to the more commonly used males. Indeed, choice of the HR lever in this study was 66%, while HR choice has ranged from 56% (Hosking, Cocker et al, 2014) to 73% (Hosking, Lam et al, 2014) across male cohorts (HR choice is typically ~70%). Accuracy and premature responding rates are also similar to those typically observed in male cohorts.…”

“…As such, improving the application or evaluation of cognitive effort may require us to look beyond the usual monoaminergic suspects typically associated with reward-related learning. Instead, cannabinoid and cholinergic receptor signalling appears to modulate rats’ willingness to put in attentional effort for more lucrative outcomes (Hosking, Lam et al, 2014; Silveira et al, 2016). Future work studying these pathways may be fruitful in identifying compounds capable of relieving anhedonia and other cognitive motivational deficits.…”

Healthy Subjects With Extreme Patterns of Performance Differ in Functional Network Topology and Benefits From Nicotine

“…The RVP and IED were selected as pre-tests since both tests were successfully used to detect behavioural changes following cholinergic manipulations, such as the administration of nicotine or cigarette smoking (Sahakian et al, 1989;Jones et al, 1992;Nesic et al, 2011). In addition, previous results also support a link between impulsiveness and nicotine effects (Hosking et al, 2014). ADHD patients with high impulsivity tend to show larger nicotine effects on response inhibition (Potter and Newhouse, 2004;Potter et al, 2012) and previous fMRI studies revealed the largest effects of nicotine on the BOLD signal during inhibitory control in individuals with high levels of impulsivity (Kasparbauer et al, 2019).…”

Neurobiological Insights Into Stress-Induced Attention Deficit

“…The NBM has strong projections to the prefrontal cortex (PFC), which enhances attention through acetylcholine binding to nicotinic receptors ( 6 ). When examining performance of this pathway in stressed rats, the authors found decreased acetylcholine output in stressed males only, matching their impaired attention.…”

“…Acetylcholine binds to both nicotinic and muscarinic receptors in the PFC. Activation of nicotinic receptors improves attention while activation of muscarinic receptors increases impulsive behaviors ( 6 ). Eck et al.…”