title: 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.
abstract: 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.
authors.affiliation: Behavioral Neuropharmacology & Neuroimaging Lab, Department of Medicine, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. thanos@bnl.gov
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
authors.forename: Michael
authors.initials: M
authors.lastname: Michaelides
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ho
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Amy H
authors.initials: AH
authors.lastname: Newman
authors.forename: Christian A
authors.initials: CA
authors.lastname: Heidbreder
authors.forename: Charles R
authors.initials: CR
authors.lastname: Ashby
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Gardner
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000818:Animals; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005449:Fluorenes / Q000008:administration & dosage / Q000494:pharmacology*; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D009765:Obesity / Q000503:physiopathology / Q000523:psychology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000502:physiology; D012054:Reinforcement, Psychology; D012646:Self Administration; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018492:Dopamine Antagonists; D005449:Fluorenes; C116818:NGB 2904; D009570:Nitriles; D010879:Piperazines; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines