Dexfenfluramine and 8-OH-DPAT modulate impulsivity in a delay-of-reward paradigm: implications for a correspondence with alcohol consumption.

Clinical studies identify impulsivity as a defining feature of an alcohol abuse syndrome. We recently reported an animal analogue: impulsivity assessed in a delay-of-reward paradigm strongly predicted magnitude of alcohol consumption. In this study we further explored this relationship. We asked whether serotonergic manipulations previously established to reduce and augment alcohol consumption would have corresponding effects on impulsivity in a delay-of-reward paradigm. This study revealed that two doses (1 and 2mg/kg) of dexfenfluramine, a serotonergic releaser known to reduce alcohol consumption, reduced choice of immediate reward, or impulsivity. We also found that three doses of the 5-HT(1A) agonist, 8-OH-DPAT, caused a biphasic dose effect on impulsivity. There was a clear dose-dependent progression from augmentation (6 and 31µg/kg) to a reduction (62µg/kg) of impulsivity scores. This effect mirrors a biphasic dose effect that has been found for alcohol intake. The findings suggest that impulsivity and alcohol consumption are intimately linked via common serotonergic pathways.