Received for publication September 18, 2006.
Revised November 15, 2006.
Accepted for publication November 16, 2006.

Cocaine Esterase: Interactions with Cocaine and Immune Responses in Mice

Abstract

Cocaine esterase (CocE) is the most efficient protein catalyst for the hydrolysis of cocaine characterized to date. The aim of this study was to investigate the in vivo potency of CocE in blocking cocaine-induced toxicity in the mouse and to assess CocE's potential immunogenicity. Cocaine toxicity was quantified by measuring the occurrence of convulsions and lethality. Intravenous administration of CocE (0.1-1 mg) 1 min prior to cocaine administration produced dose-dependent rightward shifts of the dose-response curve for cocaine toxicity. More important, i.v. CocE (0.1-1 mg), given 1 min after the occurrence of cocaine-induced convulsions, shortened the recovery time following the convulsions, and saved the mice from subsequent death. Effects of repeated exposures to CocE were evaluated by measuring anti-CocE antibody titers and the protective effects of i.v. CocE 0.32 mg against toxicity elicited by i.p. cocaine 320 mg/kg (i.e., 0-17% occurrence of convulsions and lethality). CocE retained its potency against cocaine toxicity in mice following a single prior CocE exposure (0.1-1 mg), and these mice did not show an immune response. CocE retained similar effectiveness in mice following three prior CocE exposures (0.1-1 mg/week x 3), although these mice displayed 10-fold higher antibody titers. CocE partially lost effectiveness (i.e., 33-50% occurrence of convulsions and lethality) in mice with four prior exposures to CocE (0.1-1 mg/2 weeks x 4) and these mice displayed approximately 100-fold higher antibody titers. These results suggest that CocE produces robust protection and reversal of cocaine toxicity, indicating CocE's therapeutic potential for acute cocaine toxicity. Repeated CocE exposures may increase its immunogenicity and partially reduce its protective ability.

Key words: antibodies, behavioral pharmacology, behavioral toxicology, cocaine, drug abuse, seizures