Noradrenergic regulation of cue-guided decision making and impulsivity is doubly dissociable across frontal brain regions.

Rationale: Win-paired stimuli can promote risk taking in experimental gambling paradigms in both rats and humans. We previously demonstrated that atomoxetine, a noradrenaline reuptake inhibitor, and guanfacine, a selective α2A adrenergic receptor agonist, reduced risk taking on the cued rat gambling task (crGT), a rodent assay of risky choice in which wins are accompanied by salient cues. Both compounds also decreased impulsive premature responding.

Win-Paired Cues Modulate the Effect of Dopamine Neuron Sensitization on Decision Making and Cocaine Self-administration: Divergent Effects Across Sex.

Background: Both psychostimulant use and engagement with probabilistic schedules of reward sensitize the mesocorticolimbic dopamine (DA) system. Such behaviors may act synergistically to explain the high comorbidity between stimulant use and gambling disorder. The salient audiovisual stimuli of modern electronic gambling may exacerbate the situation.

D Agonist during Learning Potentiates Cued Risky Choice.

Impulse control and/or gambling disorders can be triggered by dopamine agonist therapies used to treat Parkinson's disease, but the cognitive and neurobiological mechanisms underlying these adverse effects are unknown. Recent data show that adding win-paired sound and light cues to the rat gambling task (rGT) potentiates risky decision-making and impulsivity via the dopamine system, and that changing dopaminergic tone has a greater influence on behavior while subjects are learning task contingencies. Dopamine agonist therapy may therefore be potentiating risk-taking by amplifying the behavioral impact of gambling-related cues on novel behavior.

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.

Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity.

Gambling and substance use disorders are highly comorbid. Both clinical populations are impulsive and exhibit risky decision-making. Drug-associated cues have long been known to facilitate habitual drug-seeking, and the salient audiovisual cues embedded within modern gambling products may likewise encourage problem gambling.

Chemogenetic inhibition of dopaminergic projections to the nucleus accumbens has sexually dimorphic effects in the rat gambling task.

Women and men can differ in their propensity to take risks and develop impulse control and addiction disorders. Sexual dimorphisms in behavioral control by the mesolimbic dopaminergic reward system may underlie these phenomena, given its sensitivity to gonadal hormones. However, this is hard to test experimentally using humans.