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Substituting a long-acting dopamine uptake inhibitor for cocaine prevents relapse to cocaine seeking


Velazquez-Sanchez, C and Ferraqud, A and Ramos-Miquel, A and Canales, JJ, Substituting a long-acting dopamine uptake inhibitor for cocaine prevents relapse to cocaine seeking, Addiction biology, 18, (4) pp. 633-643. ISSN 1355-6215 (2013) [Refereed Article]

Copyright Statement

Copyright 2012 The Authors, Addiction Biology 2012 Society for the Study of Addiction

DOI: doi:10.1111/j.1369-1600.2012.00458.x


The treatment of cocaine addiction remains a challenge. The dopamine replacement approach in cocaine addiction involves the use of a competing dopaminergic agonist that might suppress withdrawal and drug craving in abstinent individuals. Although it has long been postulated that such an approach may be therapeutically successful, preclinical or clinical evidence showing its effectiveness to prevent relapse is scant. We used in rats a procedure that involved substitution of the N-substituted benztropine analog 3α-[bis(4'-fluorophenyl)methoxy]-tropane (AHN-1055), a long-acting dopamine uptake inhibitor (DUI), for cocaine. Maintenance treatment was self-administered. After extinction, reinstatement of drug seeking was induced by cocaine priming. We measured the contents of brain-derived neurotrophic factor (BDNF), c-Fos and Fas-associated death domain (FADD) proteins in the medial prefrontal cortex (mPFC) following reinstatement. DUI, but not amphetamine, substitution led to extinction of active lever presses, as did saline substitution. DUI substitution significantly reduced cocaine-induced reinstatement of drug-seeking behavior, which was strongly elicited after saline substitution. Rats passively yoked to DUI also showed reduced cocaine-primed reinstatement. Reductions in drug seeking during reinstatement were matched by downward shifts in the contents of BDNF, c-Fos and FADD proteins in the mPFC, which were elevated in relapsing rats. These data indicate that DUI substitution not only leads to extinction of self-administration behavior but also prevents reinstatement of drug seeking induced by cocaine re-exposure. Thus, DUI substitution therapy using compounds with low abuse potential, even if received passively in the context previously paired with drug taking, may provide an effective treatment for stimulant addiction.

Item Details

Item Type:Refereed Article
Research Division:Psychology
Research Group:Biological psychology
Research Field:Behavioural neuroscience
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Public health (excl. specific population health) not elsewhere classified
UTAS Author:Canales, JJ (Professor Juan Canales)
ID Code:121276
Year Published:2013
Web of Science® Times Cited:13
Deposited By:Psychology
Deposited On:2017-09-20
Last Modified:2017-10-04

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