Respective roles of dopamine D2 and D3 receptors in food-seeking behaviour in rats.
BACKGROUND
Dopaminergic mechanisms are thought to be critically involved in reward-related processes and seeking behaviour.


OBJECTIVE
To examine the involvement of dopamine in seeking behaviour supported by a natural reinforcer, food, and assess the role of D(2) and D(3) receptor subtypes in food-seeking, using an operant reinstatement procedure.


METHODS
Wistar rats were subjected to a within-session extinction procedure. Experimental sessions consisted of a 15-min rewarded period during which each right lever press delivered one food pellet and initiated a 10-s time out period (FR1:TO(10s)), followed by a 45-min extinction period during which responding was no longer rewarded. The reinstating effects of dopaminergic drugs, food priming, or the combination of both treatments, were investigated during spaced test sessions. In dose range studies, dopamine receptor ligands were administered 20 or 30 min into the test sessions. In interaction studies, antagonists were injected immediately before testing. Food priming consisted of two pellets non-contingently delivered 45 min into the test sessions.


RESULTS
Well trained rats emitted many responses during the rewarded period but almost none during extinction. During the last 15 min of the test sessions, non-rewarded responding was reinstated by the D(2)/D(3) agonist, apomorphine (0.125-0.25 mg/kg, SC), and the D(3) preferring agonist, 7-OH-DPAT (2-4 mg/kg, SC), but not by quinelorane (0.004-2 mg/kg, SC), another D(3) preferring agonist. In interaction studies, the D(2) preferring antagonist, raclopride (0.06-0.125 mg/kg, IP), and the D(3) preferring antagonist, l-nafadotride (1 mg/kg, IP), counteracted the reinstating effect of apomorphine and 7-OH-DPAT. Pellets non-contingently delivered during extinction, reinstated modest, but significant, responding. Such food-primed food-seeking was altered by neither nafadotride (0.015-1 mg/kg, IP) nor the D(2)/D(3) antagonists, amisulpride (0.25-1 mg/kg, IP) or sulpiride (2-4 mg/kg, IP). Food- and apomorphine-induced response reinstatement were additive, and food-primed food-seeking behaviour was potentiated by 7-OH-DPAT (0.125-1 mg/kg, SC) and quinelorane (7.5-15 micro g/kg, SC). Such a potentiation was reversed by two D(2) antagonists, haloperidol (0.05 mg/kg, IP) and raclopride (0.125 mg/kg, IP), but not by nafadotride (1 mg/kg, IP) and another D(3) preferring antagonist, S 33084 (0.25-2 mg/kg, SC).


CONCLUSIONS
These results indicate that reinstatement of non-reinforced responding by non-contingent food delivery and by dopamine agonists probably depend on different mechanisms. The properties of D(2)/D(3) receptor agonists, to reinstate food seeking at larger doses, and to potentiate food-primed response reinstatement at lower doses, are preferentially mediated by D(2) rather than by D(3) receptors.
Duarte
Christine
C
INSERM U.288, Faculty of Medicine Pitié-Salpêtrière, 91, Boulevard de l'Hôpital, 75634 Paris Cedex 13, France.
Biala
Grazyna
G
Le Bihan
Claudine
C
Hamon
Michel
M
Thiébot
Marie-Hélène
MH
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000077582:Amisulpride; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D050637:Receptors, Dopamine D3; D012054:Reinforcement, Psychology; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001552:Benzazepines; D001578:Benzopyrans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D009281:Naphthalenes; D011758:Pyrroles; D011759:Pyrrolidines; D011804:Quinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C408389:S 33084; D013764:Tetrahydronaphthalenes; D020891:Raclopride; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D000077582:Amisulpride; D006220:Haloperidol; C097285:nafadotride; D001058:Apomorphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; C047726:quinelorane