Abstract

When feeding is time restricted, the brain and body shift their circadian rhythms to adjust to the feeding time, a process called food entrainment. Dopamine (DA) has been suggested to play a key role in the mechanism through which food entrainment develops. Since amphetamine (AMPH) sensitization is known to enhance DA, we tested whether it would enhance behavioral output of food entrainment, called food anticipatory activity (FAA). We did not find evidence for enhancement of FAA, however, restricted feeding (RF) did result in enhanced output when measuring behavioral cross- sensitization to an acute injection of AMPH. Further investigation found that sufficient exposure to RF was necessary, for the enhancement in DA function. Cross-sensitization remained present post-RF and was not related to body weight at the time of testing, however caloric restriction was necessary. Molecular measures of DA function were examined in the dorsal striatum (DS) during RF and/ or in the re-feeding phase at which time cross-sensitization to AMPH was present. Consistent with the results of behavioral cross-sensitization, immunohistochemistry staining of dopamine transporter (DAT) in the DS revealed higher density of DAT present in rats exposed to at least two weeks of RF. No differences were found in tyrosine hydroxylase (TH) or FOS protein staining of the DS between rats exposed to RF and controls. Since one of the primary mechanisms through which AMPH acts is DAT, it is possible that the cross-sensitization in food- entrained rats may be due to an upregulation of DAT in DA fibers of the DS. Finally, since DA is known to affect mood, we examined how RF would affect behavioral measures of depression and anxiety in the rat. The results indicate that RF does not negatively affect mood and/or learning of an adaptive response to a stressor, as measured by the elevated plus maze and open-field. RF may also positively affective regulation of depression, since it results in increased swimming behavior in the forced swim test. Taken together, the findings support the role of DA in the DS as part of the food entrainment pathway and lends further support to the idea that food entrainment is a dietary regimen that does not negatively affect mental health, with possible implications for the treatment of depression.