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Psychopharmacology (Berl). 2009 Dec;207(2):281-9. doi: 10.1007/s00213-009-1653-x. Epub 2009 Sep 16.

A dopamine transport inhibitor with markedly low abuse liability suppresses cocaine self-administration in the rat.

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  • 1Biopsychology and Comparative Neuroscience Group, Cavanilles Institute (ICBiBE), University of Valencia-General Foundation & Red de Trastornos Adictivos (RETICS), Polígono de la Coma s/n, Paterna, 46980, Valencia, Spain.

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.

OBJECTIVES:

The purpose of the present experiments was to characterize in rats the addictive-like properties of one such analog, 3 alpha-[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.

PMID:
19756525
[PubMed - indexed for MEDLINE]
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