Cocaine cue-induced mesocorticolimbic activation in cocaine users: Effects of personality traits, lifetime drug use, and acute stimulant ingestion.

Stimulant drug-paired cues can acquire the ability to activate mesocorticolimbic pathways and lead to new bouts of drug use. Studies in laboratory animals suggest that these effects are augmented by progressively greater drug use histories, impulsive personality traits, and acute drug ingestion. As a preliminary test of these hypotheses in humans, we exposed cocaine users (n = 14) and healthy volunteers (n = 10) to cocaine-related videos during two functional magnetic resonance imaging (fMRI) sessions, once following acute administration of placebo and once following d-amphetamine (0.3 mg/kg, p.o.). Across sessions, cocaine users showed larger cocaine cue-induced responses than healthy controls in the associative striatum and midbrain. Among the cocaine users, larger drug cue-induced responses during the placebo session were correlated with higher Barratt Impulsiveness Scale (BIS-11) nonplanning scores (associative striatum) and greater lifetime use of stimulant drugs (limbic, associative, and sensorimotor striatum). The administration of d-amphetamine did not augment the cue-induced activations, but, in cocaine users, drug cue-induced striatal activations were more widespread following prolonged cocaine cue exposure. Together, these effects of past and present drug use might aggravate the risk for stimulant drug use problems.

Impulsive actions and choices in laboratory animals and humans: effects of high vs. low dopamine states produced by systemic treatments given to neurologically intact subjects.

Increases and decreases in dopamine (DA) transmission have both been suggested to influence reward-related impulse-control. The present literature review suggests that, in laboratory animals, the systemic administration of DA augmenters preferentially increases susceptibility to premature responding; with continued DA transmission, reward approach behaviors are sustained. Decreases in DA transmission, in comparison, diminish the appeal of distal and difficult to obtain rewards, thereby increasing susceptibility to temporal discounting and other forms of impulsive choice. The evidence available in humans is not incompatible with this model but is less extensive.