Imaging Individual Differences in Amphetamine Effects

Brown University, Providence RI

Investigators

Abstract

DESCRIPTION (provided by applicant): This project investigates the neural mechanisms of individual differences in amphetamine effects. Amphetamine has acute euphoric mood and alerting effects. These effects vary between individuals, are stable over time, and appear to be mediated by genetic factors. Recent placebo controlled studies indicate that the personality or emotional temperament of the individuals exposed to this drug play a role in these effects. To date, the personality trait of fearless sensation seeking is the strongest predictor of physiological and mood effects of amphetamine. In contrast, individual differences in the acute behavioral effects of amphetamine are less well understood, but appear to involve extraversion, a separate personality trait related to the sensitivity to reward. Thus the broad, long-term objective of the current application is to provide the empirical foundation for an in-depth study of the neural foundations of individual differences in psychostimulant drug effects using fMRI. The study utilizes a two-session, placebo-controlled amphetamine administration procedure, to provide pilot data regarding the functional alterations induced by amphetamine. Major aims are to investigate individual differences in amphetamine-induced increase in the neural activity and regions of activation associated with reward-related and punishment-related signal processing. Participants will be drawn from the extreme quartiles of scores on Tellegen's Agentic Positive Emotionality and will also vary in Harm Avoidance, which are the robust, empirically derived measures of extraversion and fearless sensation seeking that predict 40% - 50% of the variation in the acute impulsive and euphoric effects of amphetamine. Individual differences in amphetamine-induced BOLD signal will be assessed on three tasks: the Behavioral Analogue Risk Task (BART), International Affective Picture Set (lAPS), and Emotional Stroop task, in order to provide information about individual differences in the neural correlates of amphetamine effects on behavioral impulsivity, emotional reactivity, and attentional tasks that involve rewarding and punishing stimuli. In toto, the proposed pilot aims to use laboratory methods to identify neural predictors of a biobehavioral vulnerability to psychostimulant drug effects in normal populations, a goal with substantial health relevance for understanding the biological vulnerability factors for the initiation of drug use and abuse.