A dopamine transport inhibitor with markedly low abuse liability suppresses cocaine self-administration in the rat
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Other documents of the author: Ferragud, Antonio; Velázquez Sánchez, Clara; Hernández-Rabaza, Vicente; Nácher, Amparo; Merino, Virginia; Carda, Miguel; Murga, Juan; Canales, Juan José
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Show full item recordcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7053
comunitat-uji-handle3:10234/8639
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http://dx.doi.org/10.1007/s00213-009-1653-x |
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Title
A dopamine transport inhibitor with markedly low abuse liability suppresses cocaine self-administration in the ratAuthor (s)
Date
2009Publisher
Springer-VerlagISSN
0033-3158Type
info:eu-repo/semantics/articlePublisher version
http://link.springer.com/article/10.1007/s00213-009-1653-xSubject
Abstract
RATIONALE
N-substituted benztropine analogs are potent dopamine uptake inhibitors that display pharmacokinetic/dynamic properties consistent with the profile of a substitute medication for cocaine addiction.
OBJ ... [+]
RATIONALE
N-substituted benztropine analogs are potent dopamine uptake inhibitors that display pharmacokinetic/dynamic properties consistent with the profile of a substitute medication for cocaine addiction.
OBJECTIVES
The purpose of the present experiments was to characterize in rats the addictive-like properties of one such analog, 3α-[bis(4′-fluorophenyl)methoxy]-tropane (AHN-1055), incorporating probes of its stimulant and incentive/motivational effects and of its ability to influence cocaine self-administration.
METHODS
We used open field activity and drug self-administration assays. To examine the effects of AHN-1055 on locomotor behavior, the analog was administered alone (0, 1, 3, and 10 mg/kg intraperitoneally) and in combination with cocaine (15 mg/kg i.p.). The influence of AHN-1055 on cocaine's intake was studied by administering the analog (0, 3, and 10 mg/kg i.p.) before the start of the self-administration sessions. To compare the addictive-like properties of AHN-1055 and cocaine, progressive ratio performance and abstinence-induced context-conditioned relapse were evaluated.
RESULTS
AHN-1055 evoked robust and sustained locomotor activity when administered alone and increased cocaine-induced locomotor stimulation. Notably, the analog showed by comparison to cocaine weak reinforcing efficacy in a modified progressive ratio schedule of drug reinforcement, and contrary to cocaine, it showed no ability to promote context-conditioned relapse to drug seeking following stable self-administration and abstinence. Further, AHN-1055 treatment blocked cocaine intake dose-dependently in rats with a steady history of cocaine self-administration without reducing responding for sucrose, a natural reward.
CONCLUSIONS
These findings demonstrate essential psychopharmacological differences between AHN-1055 and cocaine and highlight important properties of the analog as a possible pharmacotherapy in cocaine addiction. [-]
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Psychopharmacology, 207, 2, p. 281-289Rights
© Springer-Verlag 2009
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- QUIO_Articles [690]