A critical transition in cocaine self-administration: behavioral and neurobiological implications.
BACKGROUND
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.


OBJECTIVE
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 0.008 mg.


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.
Zittel-Lazarini
Amandine
A
Laboratoire de Neuropsychobiologie, University Victor-Segalen Bordeaux 2, CNRS-UMR 5227, 146 rue Léo-Saignat, 33076, Bordeaux, France.
Cador
Martine
M
Ahmed
Serge H
SH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008962:Models, Theoretical; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration / Q000523:psychology
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine