Biobehavioral Studies of Opioid Drug Seeking Behavior

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DESCRIPTION (provided by applicant): Learning to understand, predict and control drug-seeking behavior is important to public health. Three studies described in this revised five-year R01 application will investigate the extent to which opioid drug seeking by heroin dependent volunteers can be reduced by three types of environmental factors--supplemental opioid availability, drug price, and non-drug alternatives. A choice (money versus hydromorphone [HYD]) progressive ratio task will be used to measure opioid drug seeking. Participants will be maintained on buprenorphine (to control physiological state) and studied under inpatient conditions (to control extraneous drug use). The proposed studies are significant for several reasons. First, the effects of environmental conditions on drug seeking may operate across drug classes, individuals and settings and are therefore of general importance. One such factor--drug availability--has been asserted to influence drug seeking, but there are few well-controlled tests of this hypothesis. Second, most human studies of drug seeking and behavioral economic demand (i.e. choice in the context of varying drug price and non-drug alternatives) have focused on cigarette smoking. Therefore, the proposed studies will help to assess the generality of previous findings. Third, findings from the studies will improve understanding of drug dependence mechanisms and provide empirically driven evidence for treatment and policy. Study 1 will determine whether pre-session opportunity to take "free" (unearned) supplemental HYD, i.e., an open economy, influences progressive ratio seeking of response-contingent HYD. Effects of reinforcer dose and fixed ratio values on HYD seeking will also be examined. We predict that increasing supplements to the response-contingent HYD dose will decrease HYD seeking (decrease breakpoint and increase elasticity), relative to a closed economy (no supplemental HYD). Study 2 will investigate whether post-session supplemental HYD availability (0%, 50% or 100% of the response-contingent HYD reinforcer dose) and magnitude of alternative money (wage rate: $2 [replication of Study 1] versus $4 per trial) influence drug seeking. We predict that increasing HYD supplements and the higher-magnitude money alternative will reduce HYD seeking. Study 3 will investigate whether simulated employment, unemployment and punishment differentially affect HYD seeking. Employment will be the high-magnitude money alternative from Study 2 ($4/trial with concurrent drug); Unemployment will provide concurrent drug access but no money alternative; and the Punishment condition will preclude money earnings and produce a loss of $4 for each trial that concurrent drug is chosen. These conditions will be evaluated in both closed and post-session open economies (partial replication of Study 2). We predict that employment and punishment will increase HYD demand elasticity relative to unemployment, and that these effects will be greater under open than closed economic conditions.