期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 203, 期 1, 页码 208-211出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2012.08.006
关键词
Cocaine toxicity; Anti-cocaine vaccine; Mouse; Alanine transaminase; Histopathology; Grip strength
资金
- NIDA [DP1 DA031340, R01 DA023979, R01 DA023979 S1]
- Mayo Foundation
In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination. Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice. Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120 mg/kg, i.p.). We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1 mg/kg; antibody, 8 mg/kg), they provided complete protection of liver tissue and motor function. When the enzyme levels were similar to 400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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