A critical transition in cocaine self-administration: behavioral and neurobiological implications.
Psychopharmacology. 2007-02-21; 192(3): 337-346
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RATIONALE: It has long been hypothesized that human as well as animal cocaine
users titrate their intake to maintain a specific level of cocaine reward. This
hypothesis predicts that the dose-injection function of each subject individually
should be a decreasing function, with no initial, gradual ascending limb.
OBJECTIVES: The present study was designed to test this specific prediction.
METHODS: Rats were trained to self-administer cocaine under a continuous
reinforcement schedule. After stabilization of cocaine self-administration, all
rats were tested with a wide range of i.v. cocaine doses (0.0078-1 mg). To
accurately measure the threshold dose of each individual, the pharmacological
resolution was set at 0.0078 mg at the four lowest doses.
RESULTS: As predicted, individual dose-behavior curves are discontinuous at a
threshold dose, with a descending limb but no gradual, ascending limb. Below the
threshold, there is no evidence for cocaine self-administration; at and above the
threshold, the rate of injections spikes to its maximum and then decreases
lawfully with the dose, a decrease that reflects cocaine titration. In all
individuals, this critical transition occurred over a dose interval of less than
CONCLUSIONS: This study suggests that the cumulative effects of cocaine
maintained during self-administration are all-or-nothing-a conclusion that
confirms the regulation hypothesis of cocaine reward. The neurobehavioral
consequences of this specific level of cocaine reward remain to be elucidated.
PMID: 17318508 [Indexed for MEDLINE]