QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.108.146407v1 328/3/873    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Norman, A. B. Articles by Ball, W. J. Search for Related Content PubMed PubMed Citation Articles by Norman, A. B. Articles by Ball, W. J.

NEUROPHARMACOLOGY

The Effect of a Chimeric Human/Murine Anti-Cocaine Monoclonal Antibody on Cocaine Self-Administration in Rats

Departments of Psychiatry (A.B.N., V.L.T.) and Pharmacology and Cell Biophysics (A.B.N., W.J.B.), University of Cincinnati College of Medicine, Cincinnati, Ohio; and P2D, Inc., Cincinnati, Ohio (A.B.N., M.K.N., W.R.B., M.R.T.)

The predominantly human sequence anti-cocaine monoclonal antibody (mAb), 2E2, has high affinity and specificity for cocaine and antagonizes cocaine distribution to the brain in mice. To determine whether 2E2 can alter the self-administration of cocaine in rats, both cocaine-induced reinstatement (priming) of self-administration, and the rates of cocaine consumption were assessed during daily sessions. After self-administration training, the rats' cocaine priming threshold values were stable over a 2-week baseline period. Furthermore, the rates of cocaine consumption at unit doses of 0.3 and 3.0 µmol/kg were steady within sessions and stable between sessions. Then, 2E2 (120 mg/kg i.v.) or an equivalent dose of nonspecific human polyclonal IgG (control) was infused and daily sessions continued. 2E2 produced an initial, approximately 3-fold, increase in the cocaine priming threshold that declined toward baseline values over the subsequent 3 weeks, with an effect t of approximately 4 days. In contrast to the substantial increase in the cocaine priming threshold, 2E2 produced only modest dose-dependent increases (42 and 18%) in the cocaine consumption rates, and these also gradually declined toward baseline values. There was no significant effect of the control IgG on the priming threshold or rates of consumption of cocaine. After infusion, antibody blood concentrations declined over time, and a two-compartment pharmacokinetic model generated values for the distribution and elimination half-lives of 0.5 and 11.6 days for 2E2 and 0.4 and 6.0 days for control IgG. 2E2 had a long-lasting effect on cocaine-induced priming, which may predict its efficacy as an immunotherapy for cocaine abuse.

Address correspondence to: Dr. Andrew B. Norman, Department of Psychiatry, University of Cincinnati, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0583. E-mail: andrew.norman{at}uc.edu