Assessing the initiation of cocaine self-administration in humans during abstinence: Effects of dose, alternative reinforcement, and priming

Rationale: Impaired ability to refrain from initiating cocaine-taking is a central feature of cocaine dependence and an important target for behavioral and pharmacological interventions. One potential trigger of cocaine-taking is exposure to cocaine (i.e. priming). Objective: Here, we report a model of human cocaine self-administration that quantifies the ability to refrain from initiating cocaine self-administration during abstinence and after cocaine administration. Methods: In a double-blind, within-subject, residential laboratory study, we assessed cocaine-taking as a function of the choice dose, priming dose, and the magnitude of alternative reinforcement. During each of 3 weeks, cocaine-dependent volunteers participated in one sample and three choice sessions. During sample sessions, participants were administered the dose of cocaine (0, 15 or 30 mg/ 70 kg IV) available during subsequent choice sessions that week. During choice sessions, participants chose between cocaine and decreasing amounts of money ($19, $16, $13, $10, $7, $4, $1). A priming dose of cocaine (0, 15 or 30 mg/70 kg) was administered 30 min prior to the first choice trial during each of three choice sessions each week. Results: Cocaine-taking was moderate, dose-dependent, and negatively related to the monetary alternative. An active priming injection of cocaine compared to placebo shifted choice to cocaine over money earlier in the session. Conclusions: A descending schedule of alternative reinforcement provided a measure of cocaine-taking during abstinence that was sensitive to cocaine choice dose, magnitude of alternative reinforcement, and priming. This procedure may be a useful tool for assessing potential therapies for cocaine dependence.