Evidence for the role of dopamine D3 receptors in oral operant alcohol self-administration and reinstatement of alcohol-seeking behavior in mice.

Full Abstract

The present study examined the effects of the acute intraperitoneal (i.p.) administration of the selective dopamine (DA) D(3) receptor antagonist SB-277011A (10, 20 or 30 mg/kg i.p.) on the oral operant self-administration of alcohol in male C57BL/6N mice. These effects were compared with those of naltrexone (0.5, 1 and 2 mg/kg i.p.) and acamprosate (100, 200 and 400 mg/kg i.p.). Compared with vehicle, the acute administration of SB-277011A (10 or 20 mg/kg) did not significantly alter the operant self-administration of alcohol, whereas the 30 mg/kg dose significantly reduced alcohol intake (g/kg), the number of reinforcers, and the number of active lever presses. The oral self-administration of alcohol was not significantly altered by the acute administration of either naltrexone or acamprosate, compared with vehicle-treated mice. SB-277011A, naltrexone and acamprosate were also tested in a model of drug/cue-triggered reinstatement of alcohol-seeking behavior. In this model, neither naltrexone (2 mg/kg) nor acamprosate (400 mg/kg) prevented relapse to alcohol-seeking behavior. In contrast, SB-277011A significantly reduced reinstatement of alcohol seeking in a dose-dependent manner. Provided these results can be extrapolated to humans, they suggest that selective DA D(3) receptor antagonists may be useful in the pharmacotherapeutic management of alcohol intake and prevention of relapse to alcohol-seeking behavior.

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Author information

Author/s: Heidbreder, Christian A (CA); Andreoli, Michela (M); Marcon, Cristina (C); Hutcheson, Daniel M (DM); Gardner, Eliot L (EL); Ashby, Charles R (CR);

Affiliation: Department of Neuropsychopharmacology, Centre of Excellence for Drug Discovery in Psychiatry, Verona, Italy. christian.a.heidbreder(-atsign-)gsk.com

Journal and publication information

Publication Type: Journal Article

Journal: Addiction biology (Addict Biol), published in England. (Language: eng)

Reference: 2007-Mar; vol 12 (issue 1) : pp 35-50

Dates: Created 2007/04/04; Completed 2007/05/30;

PMID: 17407496, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alcohol Deterrents - pharmacology
Alcohol Drinking - physiopathology
Alcoholism - physiopathology
Animals
Conditioning, Operant - physiology
Dose-Response Relationship, Drug
Injections, Intraperitoneal
Male

Male
Mice
Mice, Inbred C57BL
Naltrexone - pharmacology
Nitriles - pharmacology
Receptors, Dopamine D3 - antagonists & inhibitors; physiology
Taurine - analogs & derivatives; pharmacology
Tetrahydroisoquinolines - pharmacology

Associated Chemicals: Alcohol Deterrents (0) ; Nitriles (0) ; Receptors, Dopamine D3 (0) ; SB 277011 (0) ; Tetrahydroisoquinolines (0) ; Taurine (107-35-7) ; Naltrexone (16590-41-3) ; acamprosate (77337-76-9)

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