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Vol. 295, Issue 3, 1127-1134, December 2000

Natural and Artificial Enzymes Against Cocaine. I. Monoclonal Antibody 15A10 and the Reinforcing Effects of Cocaine in Rats1,2

Theodore J. Baird, Shi-Xian Deng, Donald W. Landry, Gail Winger and James H. Woods

Departments of Pharmacology (T.J.B., G.W., J.H.W.) and Psychology (J.H.W.), University of Michigan, Ann Arbor, Michigan; and Department of Medicine (D.W.L., S.-X.D.), Columbia University, College of Physicians and Surgeons, New York, New York

Recent reports have indicated the potential usefulness of anticocaine catalytic monoclonal antibodies in reducing cocaine's toxic and reinforcing effects by altering its pharmacokinetics to favor increased metabolism to the systemically inert products ecgonine methylester and benzoic acid. The present study was designed to further these findings by evaluating the hypothesis that administration of the anticocaine catalytic monoclonal antibody mAb 15A10 would dose and time dependently reduce behavior maintained by a range of doses of i.v. cocaine. Male Sprague-Dawley rats were trained in daily 8-h sessions to self-administer i.v. cocaine. A within-session multiple-dose protocol was used wherein rats were allowed access to saline or one of six doses of cocaine [0 (saline), 0.015, 0.03, 0.06, 0 (saline), 0.125, 0.25, or 0.5 mg/kg/injection] each hour in the order stated. After demonstrating stable dose-response curves over 3 consecutive days, rats were given 30-min pretreatments of saline or mAb 15A10, (10, 30, or 100 mg/kg i.v.). Antibody, but not saline, pretreatments significantly altered dose-response curves for cocaine self-administration in a dose- and time-dependent manner, resulting in downward and rightward shifts in rates of responding across the cocaine dose range. These effects were apparently not attributable to general behavioral suppression, because operant behavior for an alternative reinforcer was not likewise affected. The present data extend previous work indicating that pharmacokinetic approaches may be of worth in the search for clinically effective cocaine antagonists.

1 This work was supported by National Institute on Drug Abuse Grants DA00254 and DA07268-08. Preliminary data were presented to the College on Problems of Drug Dependence in 2000.

2 Primary laboratory of origin: James H. Woods, Ph.D., Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI 48109-0632.

0022-3565/00/2953-1127$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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