The effects of two highly selective dopamine D3 receptor antagonists (SB-277011A and NGB-2904) on food self-administration in a rodent model of obesity

In the current study, we examined the effect of the selective D(3) receptor antagonists SB-277011A and NGB 2904 on operant food self-administration (FSA) in Zucker obese and lean rats. Obese (Ob) and lean (Le) Zucker rats were maintained under a restricted feeding regimen (70% of ad-libitum rat chow...

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Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2008-06, Vol.89 (4), p.499-507
Main Authors: THANOS, Panayotis K, MICHAELIDES, Michael, HO, Christopher W, WANG, Gene-Jack, NEWMAN, Amy H, HEIDBREDER, Christian A, ASHBY, Charles R, GARDNER, Eliot L, VOLKOW, Nora D
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Conditioning, Operant
Disease Models, Animal
Dopamine Antagonists - pharmacology
Eating - drug effects
Eating - physiology
Fluorenes - administration & dosage
Fluorenes - pharmacology
Medical sciences
Metabolic diseases
Nitriles - administration & dosage
Nitriles - pharmacology
Obesity
Obesity - physiopathology
Obesity - psychology
Piperazines - administration & dosage
Piperazines - pharmacology
Rats
Rats, Zucker
Receptors, Dopamine D3 - antagonists & inhibitors
Receptors, Dopamine D3 - physiology
Reinforcement (Psychology)
Self Administration
Tetrahydroisoquinolines - administration & dosage
Tetrahydroisoquinolines - pharmacology
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Summary:In the current study, we examined the effect of the selective D(3) receptor antagonists SB-277011A and NGB 2904 on operant food self-administration (FSA) in Zucker obese and lean rats. Obese (Ob) and lean (Le) Zucker rats were maintained under a restricted feeding regimen (70% of ad-libitum rat chow) and were trained to lever press for food during daily, 2 hour fixed-ratio 4 (FR4) schedules. Once rats reached a stable baseline for FSA, they were injected with vehicle until a stable FSA criterion was achieved. Animals then received daily injections of different random doses of SB-277011A (3, 10, and 30 mg/kg i.p.), and NGB-2904 (0.3, 1 and 3 mg/kg i.p.). SB-277011A produced a significant decrease in both food intake and active lever responses in both Ob and Le rats. In contrast, NGB-2904 did not decrease food intake levels or lever presses for food in Ob and Le rats. These results suggest that along with its involvement in seeking behavior for drugs of abuse, the D(3) dopamine receptor may also be involved in seeking behavior for natural reinforcers such as food.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2008.02.003