Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage

Yang Gao, Liyi Geng, Frank Orson, Berma Kinsey, Thomas R. Kosten, Xiaoyun Shen, William Stephen Brimijoin

Research output: Contribution to journalArticle

15 Citations (Scopus)

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, 1 mg/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.

Original languageEnglish (US)
Pages (from-to)208-211
Number of pages4
JournalChemico-Biological Interactions
Volume203
Issue number1
DOIs
StatePublished - Mar 25 2013

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Viral Vaccines
Gene transfer
Viral Genes
Hydrolases
Cocaine
Liver
Toxicity
Vaccines
Enzymes
Antibodies
Butyrylcholinesterase
Cocaine-Related Disorders
Lethal Dose 50
Muscle Weakness
Locomotion
Anti-Idiotypic Antibodies
Pharmaceutical Preparations
Vaccination
Muscle
Rats

Keywords

  • Alanine transaminase
  • Anti-cocaine vaccine
  • Cocaine toxicity
  • Grip strength
  • Histopathology
  • Mouse

ASJC Scopus subject areas

  • Toxicology

Cite this

Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage. / Gao, Yang; Geng, Liyi; Orson, Frank; Kinsey, Berma; Kosten, Thomas R.; Shen, Xiaoyun; Brimijoin, William Stephen.

In: Chemico-Biological Interactions, Vol. 203, No. 1, 25.03.2013, p. 208-211.

Research output: Contribution to journalArticle

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