Respective roles of dopamine D₂ and D₃ receptors in food-seeking behaviour in rats

Abstract

Rationale. 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 D₂ and D₃ 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 D₂/D₃ agonist, apomorphine (0.125–0.25 mg/kg, SC), and the D₃ preferring agonist, 7-OH-DPAT (2–4 mg/kg, SC), but not by quinelorane (0.004–2 mg/kg, SC), another D₃ preferring agonist. In interaction studies, the D₂ preferring antagonist, raclopride (0.06–0.125 mg/kg, IP), and the D₃ 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 D₂/D₃ 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 µg/kg, SC). Such a potentiation was reversed by two D₂ antagonists, haloperidol (0.05 mg/kg, IP) and raclopride (0.125 mg/kg, IP), but not by nafadotride (1 mg/kg, IP) and another D₃ preferring antagonist, S 33084 (0.25–2 mg/kg, SC).

Conclusion. 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 D₂/D₃ receptor agonists, to reinstate food seeking at larger doses, and to potentiate food-primed response reinstatement at lower doses, are preferentially mediated by D₂ rather than by D₃ receptors.