Dopamine Is Involved in Food-Anticipatory Activity in Mice

When food is available during a restricted and predictable time of the day, mammals exhibit food-anticipatory activity (FAA), an increase in locomotor activity preceding the presentation of food. Although many studies have attempted to locate the food-entrainable circadian oscillator in the central nervous system, the pathways that mediate food entrainment are a matter of controversy. The present study was designed to determine the role of dopaminergic and histaminergic systems on FAA. Mice were given access to food for 2 h (ZT12-ZT14), and FAA was defined as the locomotor activity that occurred 2 h before the availability of food. Dopamine D1 receptor (R), D2R, and histamine H1R-specific antagonists were used to clarify the role of dopamine and histamine receptors in FAA induced by food restriction (FR). FAA was monitored by infrared locomotor activity sensors. Mice were sacrificed at ZT12 on the 14th day of FR, and monoamine concentrations were determined by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ECD). The results showed that pretreatment with the D1R antagonist SCH23390 at 1, 3, or 10 µg/kg significantly reduced FAA by 19% ( p < 0.05), 26% ( p < 0.05), or 19% ( p < 0.01), respectively, and the D2R antagonist raclopride at 22, 67, or 200 µg/kg significantly reduced FAA by 16% ( p < 0.05), 36% ( p < 0.01), or 41% ( p < 0.01), respectively, as compared with vehicle control. Moreover, coadministration of SCH23390 (10 µg/kg) and raclopride (200 µg/kg) synergistically inhibited FAA by 57% ( p < 0.01) as compared with vehicle control. Consistently, the levels of dopamine and its metabolites in the striatum and midbrain were significantly increased during FAA, even with the pretreatment of D1R and D2R antagonists. However, pretreatment with pyrilamine at 2.5, 5, or 10 mg/kg did not significantly reduce FAA, although it reduced the locomotor activity during the dark period in ad libitum mice. These results strongly indicate that the dopaminergic system plays an essential role in the FAA in mice.