Opioid and Psychostimulant Taking: Testing the Impact of Behavioral Economic Contexts

这个项目的广泛和长期目标是确定可能解释药物使用原因的因素

The broad, long-term objective of this project is to identify factors that may explain why substance use disorders occur and to identify methods for most effectively reducing drug use. Both of these goals are aligned with the mission of the National Institute on Drug Abuse. More specifically, a behavioral economic approach will be taken here to experimentally test variables that control cocaine- and opioid- taking behavior in an animal (rat) model of drug abuse. Addiction has been conceptualized as repeated, maladaptive choice of drugs over important non-drug rewards. Research in behavioral economics has found that one of the most important factors determining choice between two reinforcers (rewards) is how they interact along the substitute-to-complement continuum. If substitutes, increasing the price of one reinforcer results in reduced consumption of that reinforcer and increased consumption of the other because subjects allocate relatively more behavior to the now cheaper option. If complements, increasing the price of one reinforcer reduces consumption of both reinforcers, but, counterintuitively, subjects allocate relatively more behavior to the now more expensive option. If they are independents, then choice is relatively insensitive to price changes. Little is known about how psychostimulants like cocaine and opioids like heroin relate to non-drug alternatives in terms of substitutability/complementarity. This knowledge gap significantly limits our ability to explain, predict, or modify choice between these drugs and non-drug alternatives. This proposal will address this knowledge gap with three Specific Aims. Specific Aim 1 will test cocaine and heroin’s degree of substitution, independence, or complementarity with respect to a variety of non-drug alternatives (including both positive and negative reinforcers). Specific Aim 2 will investigate how the availability of non-drug reinforcers of varying substitutability/complementarity with cocaine and heroin affects drug value (defined in terms of behavioral economics, where value reflects how much effort subjects make to obtain the drug). Specific Aim 3 will test how these drugs’ interactions with non-drug reinforcers change on the transition from initiation/recreational use to addiction by investigating substitutability/complementarity before and after intermittent access self-administration (a procedure that produces addiction-like behavior). Completion of this research will provide important new information about factors responsible for the excessive allocation of behavior to drugs that is a hallmark of substance use disorder, a significant problem for public health today. By learning what causes excessive allocation of behavior towards drugs, we can learn how to most effectively modify behavior such that drug choice is reduced and this information can be used to improve treatments for substance use disorder.