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

Psychopharmacology (Berl). 2007 Jun;192(3):337-46. doi: 10.1007/s00213-007-0724-0. Epub 2007 Feb 21.


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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Cocaine / administration & dosage*
  • Cocaine / pharmacokinetics
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / physiopathology
  • Cocaine-Related Disorders / psychology
  • Conditioning, Operant / drug effects
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Dopamine Uptake Inhibitors / pharmacokinetics
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Models, Theoretical
  • Rats
  • Rats, Wistar
  • Reinforcement Schedule
  • Reward
  • Self Administration / psychology


  • Dopamine Uptake Inhibitors
  • Cocaine