Attenuation of sucrose reinforcement in dopamine D₁ receptor deficient mice

Abstract

Dopaminergic systems are thought to mediate the rewarding and reinforcing effects of palatable food. However, the relative contribution of different dopamine receptor subtypes is not clear. We used dopamine D1 receptor deficient mice (D1 -/-) and their wild-type and heterozygous littermates to study the role of the D1 receptor in palatable food reinforced behaviour using operant responding and free access paradigms. Non-deprived mice were trained to press a lever for sucrose pellets under three schedules of reinforcement including fixed ratios (FR-1 and FR-4) and a progressive ratio (PR). Responding on one lever was reinforced by the delivery of a sucrose pellet or solution while responding on a second lever had no programmed consequences. Initially, D1 mutant mice took longer to learn to discriminate between the two levers and had significantly lower operant responding for sucrose pellets and solution than wild-type and heterozygous mice under all schedules of reinforcement. Food deprivation enhanced responding on the active lever in all mice although it remained significantly lower in D1 -/- mice than in control mice. Following extinction of sucrose reinforcement and reversal of the levers, D1 -/- mice showed deficits in extinguishing and reversing previously learned responses. Home cage intake and preference of sucrose pellets and solutions when given under free-choice access paradigms were similar among the groups. These results suggest that the dopamine D1 receptor plays a role in the motivation to work for reward (palatable food) but not in reward perception and is critical in learning new but relevant information and discontinuing previously learned responses.

Differential Effects of Dopamine Receptor D1-Type and D2-Type Antagonists and Phase of the Estrous Cycle on Social Learning of Food Preferences, Feeding, and Social Interactions in Mice

“…It could be argued that the decreased food consumption observed in the raclopride-treated mice in the present study (Figure 4b) may be secondary to the observed reduction in activity (Supplementary Figure S2A in Supplementary Information). This would be in agreement with previous findings where feeding and motor functions of D2, but not of D1 (El-Ghundi et al, 2003), were difficult to distinguish (Caine et al, 2002;Yu et al, 2000a). However, in the present study, raclopride effects on activity were comparable to, if not lower than, those of SCH23390 (Supplementary Figures S1A and S2A in Supplementary Information), which did not cause any reductions in food intake.…”

Randomized Controlled Trials of the D1/D5 Antagonist Ecopipam for Weight Loss in Obese Subjects

“…Pre-clinical studies have shown that dopamine acting through D1 receptors decreases an animal's desire to work for food rather than the animal's desire to ingest food (42). In an experiment in which D1 receptor knockout mice exhibited reduced lever pressing for a sucrose reward, home cage sucrose consumption was similar to that of wild-type controls (20). This finding suggests that loss of D1 receptors affects motivation but not appetite.…”

Opioids for hedonic experience and dopamine to get ready for it

“…Neuroleptics injected into the nucleus accumbens of rats increased the time to reach a sucrose reward in a straight alley but do not modify the amount of sucrose consumed once it is attained (Ikemoto and Panksepp 1996). D 1 and D 2 mutant mice did not show any modification on basal food intake compared to wild-type mice when maintained on a palatable, fatenriched or sucrose diet (El-Ghundi et al 2003;. Altogether, interfering with brain dopamine neurotransmission seems to be ineffective to remove food of its primary rewarding value.…”