Pharmacological evidence that 5-HT2C receptor blockade selectively improves decision making when rewards are paired with audiovisual cues in a rat gambling task

Abstract

Rationale: Adding reward-concurrent cues to a rat gambling task (rGT) increases risky choice. This cued version of the task may reflect an "addiction-like" cognitive process, more similar to human gambling than the uncued task. Serotonergic drugs that target 5-HT₂ receptors alter mechanisms linked to impulse control. However, relatively little is known regarding the impact of such agents on either risky decision making, or the ability of conditioned stimuli to bias the choice process, despite potential relevance to addiction development and treatment.

Objectives: The aim of this study was to determine the effects of SB 242,084 and M100907, selective antagonists at the 5-HT_2C and 5-HT_2A receptors respectively, as well as the selective 5-HT_2C receptor agonist Ro-60-0175, on performance of both cued and uncued versions of the rGT.

Results: SB 242,084 significantly and dose-dependently increased choice of the most optimal option in the cued rGT only, despite concurrently increasing impulsive responses made prematurely on both the cued and uncued rGT. M100907 and Ro-60-0175 did not alter risky decision making, but nevertheless produced the expected decrease in premature responses on both task variants.

Conclusions: These findings demonstrate that the 5-HT₂ receptor-mediated regulation of risky decision making and motor impulsivity can be pharmacologically dissociated and further show that the presence of highly salient reward-paired cues critically alters the neurochemical regulation of the choice process. Importantly, these results suggest that 5-HT_2C receptor antagonists may be of use in disrupting maladaptive patterns of decision making.

Keywords: 5-HT2A; 5-HT2C; Impulsivity; Risky decision making; SB 242,084; Serotonin.