当前位置： SCI文献检索 > CHEMICO-BIOLOGICAL INTERACTIONS期刊下所有文献 > Anti-cocaine antibody and butyrylcholinesterase-derived cocaine hydrolase exert cooperative effects on cocaine pharmacokinetics and cocaine-induced locomotor activity in mice.

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

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 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.

journal_name

Chem Biol Interact

journal_title

Chemico-biological interactions

authors

Brimijoin S,Orson F,Kosten TR,Kinsey B,Shen XY,White SJ,Gao Y

doi

10.1016/j.cbi.2012.08.015

subject

Has Abstract

pub_date

2013-03-25 00:00:00

pages

212-6

issue

1

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(12)00153-6

journal_volume

203

pub_type

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