Development of an Animal Phenotype of Gambling Disorder: Chronic Reward Uncertainty Induces a Gambling Disorder-like State of Sensitization and Dysfunctional Decision-Making

Gambling Disorder (GD) is a behavioural addiction whose etiology is uncertain. Thus, it is unclear whether repeated exposure to uncertainty may induce a GD-like phenotype (indicated by dopamine (DA) sensitization and risky decision-making). Therefore, rats were trained to nose-poke on a Fixed/Variable Ratio (FR/VR) schedule of reinforcement to activate a conditioned stimulus (CS) that predicted saccharin 50/100% of time (CS50/100%). Following 66 sessions, the VR+CS100% and VR+CS50% rats demonstrated a locomotor sensitization (index of DA sensitization) to a d-amphetamine (AMPH) challenge, while only the VR+CS50% group showed impaired decision-making on the rat gambling task. To determine whether sensitization mediated impaired decision-making in the VR+CS50% group, effects of a sensitizing d-AMPH regimen on decision-making were assessed, and revealed a parallel pattern of impairment. Thus, repeated exposure to a VR schedule is implicated in a d-AMPH-like sensitization that interacted with the uncertain CS50% to mediate dysfunctional decision-making.M.Sc.2020-03-26 00:00:0