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


OBJECTIVE
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.
Kantak
K M
KM
Department of Psychology, Boston University, Massachusetts 02215, USA. kkantak@bu.edu
Collins
S L
SL
Lipman
E G
EG
Bond
J
J
Giovanoni
K
K
Fox
B S
BS
D000818:Animals; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage* / Q000276:immunology* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological; D007116:Immunization, Passive; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D014612:Vaccines; D003042:Cocaine