Abstract

Recent studies have shown that clock genes influence the expression of enzymes involved in the regulation of dopamine levels, and that reciprocally, dopamine signaling can influence the expression of several clock genes. Although many studies have looked at the response of clock genes to increases in dopamine via the use of dopamine agonists or stimulant drugs that affect dopamine release and reuptake, very few have looked at the response to decreases in endogenous dopamine. The present thesis sought to examine the effect of intracerebroventricular (i.c.v.) injection of6-0HDA on the expression of the clock gene, PERIOD2 (PER2) in the dorsal striatum and the limbic forebrain. Specifically, PER2 expression was quantified in the suprachaismatic nucleus (SCN), 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); all areas that have been previously shown to express PER2 with circadian rhythmicity. Rats that received i.c.v. 6-0HDA injections showed bilateral depletion of dopamine throughout the basal ganglia and the extended amygdala as well as a blunted rhythm ofPER2 expression in the striatum and the BNSTov. A novel rhythm ofPER2 expression was observed in the periventricular nucleus of the hypothalamus (PV) of control rats and this rhythm was blunted in 6-0HDA lesioned rats. This interaction between dopamine and clock gene expression has implications for the study of circadian disruptions in mood disorders and in parkinson's disease.