Abstract

Daily exposure to light is the most powerful means of entraining circadian rhythms of clock gene expression in the suprachiasmatic nucleus (SCN), the body's master timekeeper, and in other brain regions and peripheral tissues; however, a variety of non-photic stimuli have also been found to entrain rhythmic clock gene expression in the brain, including motivationally significant events such as stressors and rewards. The present experiments investigated the role of the neurotransmitter, dopamine (DA), in entraining the daily rhythm of the clock protein, PERIOD2 (PER2), in the SCN of the male Wistar rat, as well as in several regions of the limbic forebrain that regulate motivational states: namely, the dorsal striatum, the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), and the dentate gyrus (DG). In the dorsal striatum, the normal daily peak of PER2 expression was blunted following selective destruction of midbrain DA neurons with 6-hydroxydopamine (6-OHDA) and after blockade of D2 DA receptors with the antagonist, raclopride, whereas daily injections of a D2 agonist but not a D1 agonist restored and entrained the PER2 rhythm in the 6-OHDA-lesioned striatum. Disruption of catecholamine signaling in general using systemic injections of the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (AMPT), or daily morphine injections and withdrawal of morphine also blunted the normal PER2 peak in the dorsal striatum. Together, these results suggest that daily stimulation of D2 receptors is necessary for the striatal PER2 rhythm. In the BNSTov and CEA, daily injections of a D2 agonist or morphine increased PER2 expression near the time of injection, but other manipulations of DA signaling or catecholamines in general had no effect on PER2. In the BLA and DG, disruption of catecholamine signaling using AMPT or morphine injections blunted the normal PER2 peak in these regions but DA-selective manipulations had no effect on PER2. None of these manipulations affected the normal PER2 rhythm in the SCN. Taken together, these findings indicate that daily stimulation of 02 receptors regulates the PER2 rhythm in the dorsal striatum, and that DA does not directly contribute to the normal PER2 rhythm in the SCN or in any other forebrain region examined.