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A human anti‐cocaine monoclonal antibody antagonizes the cocaine‐induced reinstatement of self‐administration in rats
Author(s) -
Norman Andrew B.,
Norman Mantana K.,
Buesing William R.,
Tabet Michael R.,
Tsibulsky Vladimir L.,
Ball William J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.713.16
Subject(s) - self administration , medicine , pharmacology , priming (agriculture) , monoclonal antibody , cocaine abuse , antibody , anesthesia , biology , immunology , psychiatry , botany , germination
Immunotherapy may represent a viable alternative to pharmacotherapy for cocaine abuse. The predominantly human sequence anti‐cocaine monoclonal antibody, 2E2, has high affinity (Kd = 4 nM) and specificity for cocaine. In mice, 2E2 sequesters cocaine in the peripheral circulation, thereby decreasing brain cocaine concentrations. Therefore, it was hypothesized that 2E2 would antagonize cocaine‐induced reinstatement (priming) of self‐administration, a partial model of relapse that depends on the brain cocaine concentration. The level of cocaine required to reinstate self‐administration (priming threshold) in trained rats was calculated during daily sessions run 6 days a week. After 2 weeks of baseline measurements, rats were infused with 2E2 (120 mg/kg i.v.) or an equivalent dose of human polyclonal IgG as a control and daily sessions resumed. 2E2 produced a significant almost 3‐fold increase in priming threshold that gradually declined towards baseline values. The control IgG had no effect. The terminal elimination half‐life of 2E2 was 10 days. 2E2 also produced an approximately 20–40% increase in the rate of maintained cocaine self‐administration, which declined over days. This is less than the increase typically produced by competitive dopamine receptor antagonists. 2E2 may represent a therapeutic agent for decreasing the probability of relapse in cocaine abusers. Supported by PHS grant DA018538 .