Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model

Psychopharmacology (Berl). 2000 Feb;148(3):251-62. doi: 10.1007/s002130050049.


Rationale: Previous pre-clinical studies with an anti-cocaine monoclonal antibody left open several issues critical to assessing the effectiveness of a vaccine for altering cocaine self-administration behavior.

Objectives: The objectives of this study were to determine, first, whether changes in self-administration behavior would be systematically related to antibody level and, second, how the antibody affected the self-administration of different doses of cocaine.

Methods: Two experiments were conducted using a second-order schedule of drug delivery in rats. The first was a passive-administration study using the anti-cocaine monoclonal antibody MO240 to examine the relationship between antibody level and cocaine self-administration behavior, and the second was an active-immunization study to examine the efficacy of the cocaine vaccine IPC-1010 for blocking various doses of self-administered cocaine.

Results: The passive-administration experiment with control and 4-mg or 12-mg MO240 treatments showed that antagonism of the 1 mg/kg cocaine training dose was dependent on antibody level. In animals whose serum antibody levels were sustained above 0.05 mg/ml, there was a sufficient amount of antibody to reduce drug-seeking behavior and drug intake. In the active-immunization experiment, the cocaine vaccine IPC-1010 induced average serum antibody levels of 0.08 mg/ml and reduced the reacquisition of behavior by 1 mg/kg cocaine. Antagonism of cocaine self-administration after immunization was evident across a range of doses of cocaine and was only apparent in animals whose serum antibody levels exceeded 0.05 mg/ml. Furthermore, there was no evidence that the antagonism was surmountable within the dose range examined (up to 5.6 mg/kg).

Conclusions: Antagonism of cocaine self-administration across a range of doses is feasible after immunization with a cocaine vaccine as long as antibody levels are of a sufficient concentration.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / blood*
  • Antibodies, Monoclonal / immunology
  • Brain / metabolism
  • Cocaine / administration & dosage*
  • Cocaine / immunology*
  • Cocaine / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Extinction, Psychological
  • Immunization, Passive
  • Male
  • Myocardium / metabolism
  • Rats
  • Rats, Wistar
  • Reinforcement, Psychology
  • Self Administration
  • Vaccination
  • Vaccines / immunology*


  • Antibodies
  • Antibodies, Monoclonal
  • Vaccines
  • Cocaine