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.

Impulsivity predicts individual susceptibility to high levels of alcohol self-administration.

Clinical studies indicate large individual differences in susceptibility to alcohol abuse. Poor behavioral self -regulation has been proposed to reflect a predisposing factor. Like humans, only some rats regularly consume large and intoxicating amounts of alcohol. We hypothesized that clinical indications of impaired behavioral self-regulation should be reflected in an animal model of impulse control, and in this study we assessed impulsivity with a delay-of-reward paradigm. We found that three groups representing three levels of impulsivity predicted augmenting levels of alcohol self-administration. Also, overall impulsivity scores were found to be significantly correlated with magnitude of alcohol self-administration. The finding that high impulsivity is linked to elevated consumption represents an animal model that may mirror clinical depictions of an alcohol abuse syndrome. This animal model may help elucidate the neurobiological basis of individual susceptibility to alcohol addiction.