Assessing the initiation of cocaine self-administration in humans during abstinence: effects of dose, alternative reinforcement, and priming.
BACKGROUND
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 i.v.) 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.
Donny
Eric C
EC
Behavioral Pharmacology Research Unit, Johns Hopkins School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA. edonny@jhmi.edu
Bigelow
George E
GE
Walsh
Sharon L
SL
D000328:Adult; D002755:Choice Behavior; D003042:Cocaine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D012054:Reinforcement, Psychology; D012646:Self Administration; D019966:Substance-Related Disorders / Q000503:physiopathology / Q000523:psychology*
D003042:Cocaine