Anti-cocaine antibody and butyrylcholinesterase-derived cocaine hydrolase exert cooperative effects on cocaine pharmacokinetics and cocaine-induced locomotor activity in mice

Stephen Brimijoin, Frank Orson, Thomas R. Kosten, Berma Kinsey, Xiao Yun Shen, Sarah J. White, Yang Gao

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

We are investigating treatments for cocaine abuse based on viral gene transfer of a cocaine hydrolase (CocH) derived from human butyrylcholinesterase, which can reduce cocaine-stimulated locomotion and cocaine-primed reinstatement of drug-seeking behavior in rats for many months. Here, in mice, we explored the possibility that anti-cocaine antibodies can complement the actions of CocH to reduce cocaine uptake in brain and block centrally-evoked locomotor stimulation. Direct injections of test proteins showed that CocH (0.3 or 1 mg/kg) was effective by itself in reducing drug levels in plasma and brain of mice given cocaine (10 mg/kg, s.c., or 20 mg/kg, i.p). Administration of cocaine antibody per se at a low dose (8 mg/kg, i.p.) exerted little effect on cocaine distribution. However, a higher dose of antibody (12 mg/kg) caused peripheral trapping (increased plasma drug levels), which led to increased cocaine metabolism by CocH, as evidenced by a 6-fold rise in plasma benzoic acid. Behavioral tests with small doses of CocH and antibody (1 and 8 mg/kg, respectively) showed that neither agent alone reduced mouse locomotor activity triggered by a very large cocaine dose (100 mg/kg, i.p.). However, dual treatment completely suppressed the locomotor stimulation. Altogether, we found cooperative and possibly synergistic actions that warrant further exploration of dual therapies for treatment of cocaine abuse.

Original languageEnglish (US)
Pages (from-to)212-216
Number of pages5
JournalChemico-biological interactions
Volume203
Issue number1
DOIs
StatePublished - Mar 25 2013

Keywords

  • Brain cocaine
  • Locomotor stimulation
  • Metabolism and distribution
  • Therapeutic antibody

ASJC Scopus subject areas

  • Toxicology

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