Dopamine D1 Receptor-Mediated Regulation of Per1, Per2, CLOCK, and BMAL1 Expression in the Suprachiasmatic Nucleus in Adult Male Rats

Abstract

Photic and non-photic inputs are reported to affect clock gene expressions and behavioral activities in the SCN. However, it is not known whether dopaminergic input mediates these regulatory effects on clock genes. The present study examined the molecular effects of dopamine D1 agonist on Per1, Per2, CLOCK, and Bmal1 expressions in the SCN and its effect on behavioral activities to determine the role of dopamine D1 receptor in regulation of these gene expressions and behavioral activities in adult male Wistar rats. To examine the molecular effects of dopamine D1 agonist day and night, we injected 20 mg/kg SKF38393 to the first group of rats at 6 a.m. and the second group at 6 p.m. We also injected saline to the third and fourth groups of rats at 6 a.m. and 6 p.m. as control groups. All rats were sacrificed 2 h following the injections. The real-time PCR technique was used to evaluate the clock gene expression. In addition, to examine the effects of dopamine D1 agonists on behavioral activities, we injected 20 mg/kg SKF38393 to SKF receiving group and saline to control group. The behavioral activities of the rats were monitored on the running wheel for 21 days, 1 week following the injections. SKF injections increased the Per2 and CLOCK expressions in the daytime and significantly decreased the Per1 and Bmal1 expressions. However, at night, SKF injections increased only Per2 expressions significantly and decreased the Per1, CLOCK, and Bmal1 genes expressions. Both saline receiving groups showed that all gene expressions were significantly higher except Per2 during nighttime. SKF injection increased the running wheel activity during nighttime significantly. Based on the obtained result, clock gene expression and behavioral activities in adult male Wistar rats may be altered or monitored by administration of exogenous dopamine.

Keywords: Bmal1; CLOCK; Circadian rhythm; Dopamine D1 receptor; Per1; Per2; Suprachiasmatic nucleus.