Opioid abuse, including abuse of prescription opioid medications, has become a significant health concern. One concern is that it is associated with an increased likelihood of impulsive and risky behaviors; these behaviors place individuals at risk of contracting and transmitting diseases such as HIV/AIDS and at risk of continued drug abuse, which can increase the chances of dependence and overdose. Although impulsivity is a determinant of substance abuse, evidence indicates that it also is an outcome of substance abuse (i.e., substance abuse can produce impulsive and risky behavior). Although pre-clinical research investigating effects of abused drugs on impulsive and risky behavior has grown recently, there are significant gaps in our knowledge about the specific behavioral mechanisms involved in those effects. Growing evidence indicates that impulsive and risky choices are the result of behavioral processes that contribute to reward value. Less is known about precisely how drugs, particularly opioids, affect specific dimensions that determine reward value. Reward value is a composite measure of several dimensions, including its size (magnitude), the delay to its receipt (delay), and the likelihood that the reward actually will be received (probability). The central hypothesis is that understanding how drugs affect the specific dimensions of reward value is crucial for understanding their effects on impulsive and risky behavior. Thus, the overall goal is to utilize innovative laboratory-animal models to characterize how both acute and chronic exposure to, and withdrawal from, the prescription opioid oxycodone affect specific reward processes involved in impulsive and risky behavior. This goal will be accomplished by addressing two specific aims. 1) Isolate and quantify effects of acute and chronic exposure to and withdrawal from oxycodone on the specific reward mechanisms of impulsive choice. 2) Isolate and quantify effects of acute and chronic exposure to and withdrawal from oxycodone on the specific reward mechanisms of risky choice. This proposal is innovative in that it utilizes specialized experimental methods that identify the specific reward dimensions involved in oxycodone's effects on impulsive and risky choices, and employs data-analytic methods to quantify the relative impact of oxycodone on each reward dimension. The proposed research is significant because it will provide critical information on the behavioral mechanisms involved in effects of oxycodone on impulsive and risky behavior that will fill gaps in our current knowledge, help inform investigations of underlying neurobiological mechanisms, and facilitate the development therapeutic interventions that are based upon the identified reward mechanisms.
The proposed project is relevant to public health by identifying behavioral mechanisms that mediate the effects of substance abuse on impulsive and risky behaviors. This research is relevant to NIH's mission by seeking fundamental knowledge about the adverse effects of substance abuse. This knowledge will inform translational efforts to reduce the health and economic burdens associated with substance abuse.
