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Therapeutic-like properties of a dopamine uptake inhibitor in animal models of amphetamine addiction

Citation

Velazquez-Sanchez, C and Ferragud, A and Renau-Piqueras, J and Canales, JJ, Therapeutic-like properties of a dopamine uptake inhibitor in animal models of amphetamine addiction, International Journal of Neuro-Psychopharmacology, 14, (5) pp. 655-665. ISSN 1461-1457 (2011) [Refereed Article]

Copyright Statement

Copyright 2010 CINP

DOI: doi:10.1017/S1461145710000969

Abstract

N-substituted benztropine (BZT) analogs are molecules that display high affinity for the dopamine transporter (DAT), therapeutic-like effects in animal models of cocaine abuse, and psychopharmacological characteristics consistent with those of a substitute medication for cocaine addiction. Since amphetamine (Amph) and cocaine share mechanisms of action at the DAT, we evaluated the effectiveness of a BZT analog in animal models of Amph addiction. We tested in mice and rats the effects of the BZT derivative, 3α-[bis(4-fluorophenyl)methoxy]-tropane (AHN-1055), on Amph-induced conditioned place preference (CPP), locomotor activity, sensitization, self-administration and ΔFosB accumulation in the nucleus accumbens (NAc). The results showed that AHN-1055 did not produce rewarding, stimulant, or sensitized locomotor effects in mice when administered alone but it readily blocked the rewarding, stimulant, and sensitizing effects of repeated Amph exposure. Furthermore, in mice undergoing conditioning in the CPP paradigm, the BZT analog prevented the accumulation of ΔFosB protein induced in the NAc shell region by Amph treatment. Notably, treatment with AHN-1055 dose-dependently reduced Amph self-administration in rats with a steady history of voluntary Amph intake. These results provide a straightforward demonstration that a BZT derivative with binding affinity for DAT exhibits high efficacy in animal models of Amph abuse, suggesting that the novel generation of BZT analogs could have wider therapeutic applications in stimulant-spectrum disorders than those previously recognized.

Item Details

Item Type:Refereed Article
Research Division:Psychology and Cognitive Sciences
Research Group:Psychology
Research Field:Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Substance Abuse
Author:Canales, JJ (Professor Juan Canales)
ID Code:121300
Year Published:2011
Web of Science® Times Cited:12
Deposited By:Psychology
Deposited On:2017-09-21
Last Modified:2017-10-18
Downloads:0

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