Modafinil increases reward salience in a slot machine game in low and high impulsivity pathological gamblers.

This study examined the effects of modafinil (200 mg) on slot machine betting profiles from a previous sample of low and high impulsivity (LI/HI) pathological gamblers (10/Group; Zack and Poulos, 2009). Hierarchical regression assessed the prospective relationship between Payoff and Bet Size on consecutive trials, along with moderating effects of Group, Cumulative Winnings (low/high) and Phase of game (early/late) under drug and placebo. Y intercepts for the simple regressions of Bet Size on Payoff indexed overall motivation to bet. Under placebo, both groups gauged their bets less closely to the preceding Payoff as trials continued when Winnings were low but not high. Under modafinil, both groups gauged their bets more closely to the preceding Payoff when Winnings were low but gauged their bets less closely to the previous Payoff when Winnings were high. The tendency to gauge bets closely to the previous Payoff coincided with a bias toward low overall Bet Size, and modafinil accentuated this relationship, in LI but not HI subjects. Results suggest that modafinil increases the salience of environmental rewards, leading to more tightly calibrated responses to individual rewards when resources are low, but progressively loosens reward-response calibration when resources are high. Increased relative impact of phasic vs. tonic dopamine signals may account for patterns seen at low vs. high Winnings, respectively, under the drug. Clinically, modafinil may deter pathological gamblers from chasing losses but also encourage them to continue betting rather than quit while they are ahead. Whether low-dose modafinil confers more uniform benefits deserves investigation.