|
Projects
Project 1: Individual Differences in Drug Response: An Animal Model | Abstract: Recent theories describe drug abuse as a disorder involving not only positive incentive motivation, but as a disorder also charactered by a loss of inhibitory control. In this project, we will use a laboratory animal model to determine the critical neural mechanisms that underlie the association between risk-related traits and drug abuse, questions that cannot be addressed fully using human subjects. Our working hypothesis is that individual differences in the risk-related traits, reward seeking and inhibition, play a role in drug abuse vulnerability and that individual differences in these two behavioral constructs are mediated by dissociable neural systems. While reward seeking and inhibition undoubtedly involve complex and overlapping neural circuits, our current knowledge suggests that reward seeking is subserved by ascending mesocorticolimbic dopamine (DA) systems, whereas inhibition is subserved by frontal cortical regions involving both DA and serotonin (5-HT). Anatomical studies have also revealed that the medial prefrontal cortex (mPFC) is implicated in both reward seeking and inhibition, whereas the orbitofrontal cortex (OFC) is implicated in inhibition. These neural systems will be examined to determine their role in the association of reward seeking and inhibition with drug reward. Rats will be assessed for individual differences in reward seeking and inhibition using a variety of behavioral tests and then will assessed for amphetamine reward, DA and 5-HT transporter function, and neural activity assessed by in vivo voltammetry and electrophysiological studies. We predict that rats that are high in reward seeking and low in inhibition will be most vulnerable to the rewarding effect of amphetamine and related drugs. Also, we predict that rats that are high in reward seeking and low in inhibition will be most sensitive to nondrug alternative reinforcers that compete with drug reward, which may have important translational implications for the design of effective drug abuse prevention intervention strategies in humans. Finally, we predict that individual differences in reward seeking and inhibition will be associated with differences in DA and 5-HT systems within the nucleus accumbens, mPFC and/or OFC. These results, combined with the human behavioral pharmacology and neuroimaging results in Project 2, will provide a more comprehensive understanding the neural systems involved in risk-related traits relevant to the design of tailored anti-drug prevention intervention messages.
| Project 2: Drug Abuse Liability and Sensation-Seeking Status | Abstract: Prevention investigators in our Center and elsewhere have demonstrated that drug abuse prevention efficacy can be significantly enhanced by targeting individuals who are most vulnerable to developing problems and tailoring message content and format based on the characteristics of these individuals. Further development of laboratory models to identify individuals who are vulnerable to developing regular and problematic patterns of drug use and identifying the characteristics of these individuals that predispose them to vulnerability and/or influence the efficacy of communication/education programs is of critical importance for informing and advancing the field of drug abuse prevention.
This application proposes five years of research to continue laboratory investigations of individual differences associated with drug abuse vulnerability. Prior epidemiological research has established a link between the biologically-based personality trait of sensation-seeking (or novelty-seeking) and drug abuse in humans. Research with rat models suggests that novelty-seeking behavior is predictive of individual differences in dopamine function and in the reinforcing and other behavioral effects of drugs of abuse. Our recent clinical laboratory studies demonstrate an association between sensation seeking and individual differences in both brain function and in the reinforcing and other behavioral effects of drugs of abuse. Sensation seeking consists of dissociable biologically-based dimensions of reward seeking and inhibition; each of these dimensions has been postulated to play an important role in determining drug abuse vulnerability via distinct and separable biobehavioral mechanisms. A multidisciplimary approach combining laboratory abuse liability assessment and brain imaging methodologies will be used to examine the separate and combined effects of reward seeking and inhibition traits on 1) drug abuse vulnerability, 2) brain responses associated with reward and inhibition processing, 3) brain responses associated with drug effects on reward and inhibition processing, and 4) brain responses to emotional and novel stimulus materials. These studies will support the development of more efficacious prevention interventions by defining individual characteristics and associated brain processes that are linked to drug abuse vulnerability that can be used to improve the precision of targeted and tailored programs.
| Project 3: Interventions Informed by Individual Differences | Abstract: To optimally design targeted interventions aimed at reducing substance use, one must know which characteristics or traits are involved in substance use and how these characteristics lead to substance use; these relations are likely to be complex and to involve bi-directional influences. The present project focuses on two separable traits related to substance use: reward seeking, defined as a tendency to enjoy and pursue exciting activities and new experiences, and low inhibition, defined as the tendency to act without thinking or reflection. The research primarily examines basic, elemental processes (e.g., risk tolerance, inhibitory control, delay discounting, Behavioral Inhibition or Activation System functioning) that may mediate the relations between these traits and substance use. The elemental processes are hypothesized to reflect the activity of two biological systems: an approach/reward seeking system and an inhibitory system. The reward system is theorized to be responsive to reward and is responsible for activating approach behavior. The inhibition system is theorized to be sensitive to punishment and is responsible for inhibiting ongoing behavior and initiating active information processing. Several potential social variables are also examined as potential mediators (i.e., substance use expectancies and peers). The research also allows for the possibility that substance use itself changes the traits and the underlying elemental processes. Finally, the project examines the interrelations among the elemental processes themselves. All of these issues are examined in the context of a three-year, two cohort, longitudinal study. There are four specific aims:
1. To identify the mechanisms underlying the relations leading from reward seeking and inhibition to substance use. Inhibition and reward seeking are distinct traits with distinct outcomes including substance use and abuse. Little is known, however, about the processes that link these traits to their outcomes.
2. To examine the effect of substance use on the processes associated with reward seeking and inhibition. Research has shown acute effects of drug exposure on the processes under study. For example, alcohol has been shown to have acute effects on inhibitory control. Additionally, a number of studies have demonstrated process deficits in substance abusers. Thus, it is possible that drug use influences the processes underlying reward seeking and inhibition, although this has not been demonstrated longitudinally.
3. To examine the relations among the underlying processes themselves. The processes examined in the present research come from a variety of levels and modes of assessment, ranging from elementary inhibitory control through Behavioral Inhibition System functioning assessed via psychophysiology. Although each task and measure is related to substance use and has been designed to assess one of the two hypothetical systems, these tasks have not been examined together previously.
| Project 4: Targeting individuals with biologically-based predispositions to engage in risky behavior | Abstract: Interventions to prevent or reduce substance use or abuse among young adults are few and generally not effective. This is unfortunate, as young adults are among the most frequent users of a variety of substances, including marijuana, alcohol, and various illicit substances. Most substance abuse preventive interventions have largely ignored biologically-based predispositions that lead individuals both to engage in risky behaviors including substance use and to attend and respond to certain kinds of intervention messages. This project builds on our previous work using sensation seeking to target and tailor messages aimed at reducing substance use and risky sexual behavior. Specifically, building on emerging research from the Center, we decompose sensation seeking into its component parts of reward-seeking and inhibition. Drawing on recent advances in message targeting and tailoring, we move beyond our previous work on message sensation value to include consideration of the influence of message framing and fear on message effectiveness. The present proposal offers and tests a general model of message effectiveness that considers the interaction between individual differences (i.e., reward seeking and inhibition) and message characteristics (i.e., message sensation value, framing, and fear). The model is tested in three studies using public service announcements (PSA), an intervention mode with which our team has extensive experience.
There are four specific aims: 1) To examine the persuasive effects of high vs. low sensation value (HSV vs. LSV) substance abuse prevention messages on young adults varying in reward seeking and inhibition;
2) To examine the persuasive effects of two emotion-based dimensions of substance abuse messages: message framing (gain vs. loss-framed [GF vs. LF]) and fear (high vs. low threat [HT vs. LT]) on young adults varying in their levels of reward seeking and inhibition.; 3) To assess the extent to which the differential persuasive effects of HSV vs. LSV, GF vs. LF, and LT vs. HT substance abuse prevention messages generalize to another high-risk behavior, risky sex; and 4) Develop and pilot-test the effectiveness of substance abuse prevention public service announcements (PSAs) with young adults who are either high in reward seeking, low in inhibition, or both. We propose to accomplish these aims through three studies. The first examines the impact of message sensation value, framing, and fear on message effectiveness for PSAs aimed at reducing marijuana use as a function of reward seeking and inhibition; the second tests the boundaries of our model using PSAs aimed at reducing risky sexual behavior; the third begins the process of designing optimally effective PSAs based on previous results. Outcomes from the experiments and qualitative studies proposed in this project may be immediately applied to an established body of work, both ours and others, in the development of PSAs that are targeted at the reduction of marijuana use.
|
|