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.