Disentangling prediction error and value in a formal test of dopamine's role in reinforcement learning.

The discovery that midbrain dopamine (DA) transients can be mapped onto reward prediction errors (RPEs), the critical signal that drives learning, is a landmark in neuroscience. Causal support for the RPE hypothesis comes from studies showing that stimulating DA neurons can drive learning under conditions where it would not otherwise occur. However, such stimulation might also promote learning by adding reward value and indirectly inducing an RPE.

Increased risky choice during forced abstinence from fentanyl on the cued rat gambling task.

Rationale: The use of illicit opioids has arguably never been more risky; street drug potency can be dangerously high, is often unknown to the consumer, and results in multiple daily fatalities worldwide. Furthermore, substance use disorder (SUD) is associated with increased maladaptive, risky decisions in laboratory-based gambling tasks. Animal studies can help determine whether this decision-making deficit is a cause or consequence of drug use.

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.