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

Chem Biol Interact. 2013 Mar 25;203(1):212-6. doi: 10.1016/j.cbi.2012.08.015. Epub 2012 Aug 31.


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 1mg/kg) was effective by itself in reducing drug levels in plasma and brain of mice given cocaine (10mg/kg, s.c., or 20mg/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 (100mg/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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Brain
  • Butyrylcholinesterase / genetics
  • Butyrylcholinesterase / metabolism*
  • Cocaine / antagonists & inhibitors*
  • Cocaine / immunology*
  • Cocaine / metabolism
  • Cocaine / toxicity
  • Cocaine-Related Disorders / physiopathology
  • Cocaine-Related Disorders / therapy
  • Drug-Seeking Behavior
  • Humans
  • Hydrolases / genetics
  • Hydrolases / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Vaccines / administration & dosage


  • Antibodies
  • Recombinant Proteins
  • Vaccines
  • Hydrolases
  • Butyrylcholinesterase
  • Cocaine