Noradrenergic contributions to cue-driven risk-taking and impulsivity

Rationale The flashing lights and sounds of modern casinos are alluring and may contribute to the addictive nature of gambling. Such cues can have a profound impact on the noradrenaline (NA) system, which could therefore be a viable therapeutic target for gambling disorder (GD). While there is substantial evidence to support the involvement of NA in the impulsive symptoms of GD, its function in mediating the "pro-addictive" impact of cues is less understood. Objective We wished to investigate the role of NA in our rodent assay of decision making and impulsivity, the cued rat gambling task (crGT). Given that sex differences are prominent in addiction disorders, and increasingly reported in the monoaminergic regulation of behaviour, we also prioritised evaluating noradrenergic drugs in both sexes. Methods Female and male rats were trained to stability on the crGT and then given intraperitoneal injections of the noradrenaline reuptake inhibitor atomoxetine, the alpha(2A) receptor agonist guanfacine, the beta receptor antagonist propranolol, and the alpha(2) receptor antagonist yohimbine. Results Atomoxetine dose-dependently improved decision-making score. Guanfacine selectively enhanced decision making in risk-preferring males and optimal performing females. Propranolol and yohimbine did not influence decision making. Atomoxetine and guanfacine reduced premature responses, while yohimbine bi-phasically affected this index of motor impulsivity. Conclusions These results support the hypothesis that NA is an important neuromodulator of the cue-induced deficits in decision making observed in laboratory-based gambling paradigms, and suggest that NAergic drugs like atomoxetine and guanfacine may be useful in treating GD.