title: Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage.
abstract: 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, 1mg/kg; antibody, 8 mg/kg), they provided complete protection of liver tissue and motor function. When the enzyme levels were ~400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Liyi
authors.initials: L
authors.lastname: Geng
authors.forename: Frank
authors.initials: F
authors.lastname: Orson
authors.forename: Berma
authors.initials: B
authors.lastname: Kinsey
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Shen
authors.forename: Stephen
authors.initials: S
authors.lastname: Brimijoin
mesh_terms: D000818:Animals; D002091:Butyrylcholinesterase / Q000235:genetics / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism* / Q000633:toxicity; D019970:Cocaine-Related Disorders / Q000628:therapy; D000229:Dependovirus / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053580:Muscle Strength; D051381:Rats; D014612:Vaccines / Q000494:pharmacology*
chemical_list: D014612:Vaccines; D006867:Hydrolases; D002091:Butyrylcholinesterase; D003042:Cocaine