Cocaine hydrolase encoded in viral vector blocks the reinstatement of cocaine seeking in rats for 6 months

Justin J. Anker, William Stephen Brimijoin, Yang Gao, Liyi Geng, Natalie E. Zlebnik, Robin J. Parks, Marilyn E. Carroll

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Cocaine dependence is a pervasive disorder with high rates of relapse. In a previous study, direct administration of a quadruple mutant albumin-fused butyrylcholinesterase that efficiently catalyzes hydrolysis of cocaine to benzoic acid and ecgonine methyl ester acutely blocked cocaine seeking in an animal model of relapse. In the present experiments, these results were extended to achieve a long-duration blockade of cocaine seeking with a gene transfer paradigm using a related butyrylcholinesterase-based cocaine hydrolase (CocH). Methods: Male and female rats were allowed to self-administer cocaine under a fixed-ratio 1 schedule of reinforcement for approximately 14 days. Following the final self-administration session, rats were injected with CocH vector or a control injection (empty vector or saline), and their cocaine solutions were replaced with saline for 14 days to allow for extinction of lever pressing. Subsequently, they were tested for drug-primed reinstatement by administering intraperitoneal injections of saline (S), cocaine (C) (5, 10, and 15 mg/kg), and d-amphetamine according to the following sequence: S, C, S, C, S, C, S, d-amphetamine. Rats then received cocaine-priming injections once weekly for 4 weeks and, subsequently, once monthly for up to 6 months. Results: Administration of CocH vector produced substantial and sustained CocH activity in plasma that corresponded with diminished cocaine-induced (but not amphetamine-induced) reinstatement responding for up to 6 months following treatment (compared with high-responding control animals). Conclusions: These results demonstrate that viral transfer of CocH may be useful in promoting long-term resistance to relapse to cocaine addiction.

Original languageEnglish (US)
Pages (from-to)700-705
Number of pages6
JournalBiological Psychiatry
Volume71
Issue number8
DOIs
StatePublished - Apr 15 2012

Fingerprint

Hydrolases
Cocaine
Butyrylcholinesterase
Cocaine-Related Disorders
Dextroamphetamine
Recurrence
Reinforcement Schedule
Injections
Benzoic Acid
Self Administration
Amphetamine
Intraperitoneal Injections
Albumins
Hydrolysis
Animal Models

Keywords

  • Addiction
  • butyrylcholinesterase
  • cocaine
  • cocaine hydrolase
  • gene therapy
  • prevention
  • relapse

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Cocaine hydrolase encoded in viral vector blocks the reinstatement of cocaine seeking in rats for 6 months. / Anker, Justin J.; Brimijoin, William Stephen; Gao, Yang; Geng, Liyi; Zlebnik, Natalie E.; Parks, Robin J.; Carroll, Marilyn E.

In: Biological Psychiatry, Vol. 71, No. 8, 15.04.2012, p. 700-705.

Research output: Contribution to journalArticle

Anker, Justin J. ; Brimijoin, William Stephen ; Gao, Yang ; Geng, Liyi ; Zlebnik, Natalie E. ; Parks, Robin J. ; Carroll, Marilyn E. / Cocaine hydrolase encoded in viral vector blocks the reinstatement of cocaine seeking in rats for 6 months. In: Biological Psychiatry. 2012 ; Vol. 71, No. 8. pp. 700-705.
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