| 2003 — 2010 |
White, Tara L |
R01Activity Code Description:
To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R03Activity Code Description:
To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Imaging Individual Differences in Amphetamine Effects
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.
|
0.958 |
| 2011 — 2013 |
White, Tara L |
R21Activity Code Description:
To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Imaging Individual Differences in Methamphetamine Effects
DESCRIPTION (provided by applicant): This R21 investigates brain responses to methamphetamine (METH) in a sample of 24-30 healthy volunteers aged 18-35. Background: Methamphetamine (METH) produces behavioral and subjective activation via its acute effects on monoamines, particularly dopamine and serotonin. Unlike other psychostimulants, such as d- amphetamine, METH produces a large, sustained serotonin increase after consumption. Use and misuse of METH is an increasing public health problem. In the last decade, METH usage has surged in a west to east pattern, with large numbers of young adults reporting recreational use of street-, black-market- and prescribed- methamphetamines. Despite these trends, there has been very little actual study of the impact of METH on brain responses after drug consumption that would assist in understanding specific vulnerability factors for METH use and misuse. The present study begins to fill this gap, collecting preliminary data on fMRI brain responses to METH in a sample of healthy volunteers. Overall experimental approach / design: The project utilizes functional magnetic resonance imaging (fMRI) to investigate the neural correlates of METH exposure, using a within-subjects, counterbalanced, placebo-controlled METH administration procedure (20 mg oral) in N=24-30 healthy prescreened volunteers. The proposal includes an amphetamine condition (20 mg oral), which serves as a positive control to identify unique responses to METH compared to AMP within-subjects. We expect elevated METH effects on brain responses to reward and punishment due to serotonergic impact of METH, and the modulation of these effects by a personality trait known to relate to between-subject differences in the sensitivity of ascending serotonin systems (i.e., Trait impulsivity;Depue &White, 2009). The project has impact and significance for public health because it 1.) documents with fMRI where and how brain systems of potentially vulnerable individuals are most sensitive to METH;2.) identifies the types of brain processes most altered in these individuals, and 3.) provides evidence that can be used to guide targeted prevention efforts to reduce METH use and misuse in young adults. PUBLIC HEALTH RELEVANCE: The study is relevant to public health as it informs neural risk factors for the vulnerability to methamphetamine effects in normal populations, which may assist in better understanding and preventing the significant public health problem of methamphetamine use and dependence in healthy and addicted populations.
|
0.958 |