The Roles of Nicotinic and Muscarinic Cholinergic Receptors in Risky and Impulsive Decision Making

Abstract

Psychopathological conditions in which decision making is impaired are common and include schizophrenia, attention deficit hyperactivity disorder, and addiction, among others. This dissertation aimed to investigate the role of cholinergic signaling in risky and impulsive decision making. Rats were trained in either a “probability discounting” task in which they chose between small guaranteed and large probabilistically delivered food rewards (a measure of risky decision making), or a “delay discounting” task in which they chose between small immediate and large delayed food rewards (a measure of impulsive decision making). Rats were also divided into high and low “risk-taking” or “impulsive” groups on the basis of their performance in the tasks. Experiments 1 and 2 examined the effects of cholinergic drugs on performance in the probability and delay discounting task, respectively. In Experiment 1, acute administration of the acetylcholinesterase inhibitor donepezil decreased choice of the large risky reward in “risk-taking” rats. Acute administration of nicotine increased choice of the large risky reward in both groups, whereas administration of the nicotinic receptor antagonist mecamylamine decreased choice of the large risky reward in “risktaking” rats. In Experiment 2, nicotine increased choice of the large delayed reward and mecamylamine shifted impulsive choice in a non-specific manner in “impulsive” rats. The muscarinic receptor agonist oxotremorine decreased choice of the large delayed reward in “non-impulsive” rats and increased choice in “impulsive” rats, while treatment with the muscarinic receptor antagonist atropine increased impulsive choice in all rats. In Experiment 3, another group of rats was used to examine correlations between baseline performance in both discounting tasks and nicotinic receptor density levels in several brain regions. Impulsive choice was positively correlated with α4β2 receptor levels in ventral hippocampus and nucleus accumbens shell, and α7 receptor levels in the basolateral amygdala, such that greater impulsivity was associated with higher receptor levels. Additionally, risky choice was negatively correlated with α4β2 receptor levels in nucleus accumbens shell, such that greater risk was associated with lower receptor levels. These experiments suggest that cholinergic receptors are involved in cost-benefit decision making and that they may prove a useful target for treatment of psychopathological conditions in which decision-making deficits are present.