Exogenous corticosterone restores rhythmic expression of the clock gene, PER2, in the central extended amygdala in adrenalectomized rats

The presence of circadian oscillators in the central nucleus of the amygdala (CEA) and the oval nucleus of the bed nucleus of the stria terminalis (BNST-OV), structures that are important in stress and homeostatic responses, has recently been revealed using immunocytochemistry for the clock gene protein Period 2 (PER2). Clocks have also been discovered in the basolateral amygdala (BLA) and the hippocampus (HIPP), areas important in learning and memory, and emotion. The circadian master clock in the suprachiasmatic nucleus (SCN) drives the daily corticosterone rhythm, but does not itself have any glucocortocoid receptors and, along with the BLA and HIPP, is unaffected by adrenalectomy. In contrast, the rhythms of PER2 in the BNST-OV and CEA, normally the same as that of the SCN, are severely attenuated by adrenalectomy. To determine the role of the rat adrenal hormone corticosterone (CORT) in modulating rhythmic PER2 expression in these areas, we placed adrenalectomized (ADX) rats on one of two CORT replacement schedules: a subcutaneous 30 day time-release CORT pellet (100mg), which provided constant basal levels of 50ng/ml over a period of two weeks, or a circadian rhythm of CORT, with levels peaking at the onset of activity at an average of 11.058 µg/dl, which was achieved by providing CORT in the drinking water at a concentration of 25mg/l. Results indicate that a CORT rhythm is required for complete restoration of rhythmic PER2 expression in the CEA and BNST-OV, implicating CORT as a potential factor in synchronizing peripheral oscillators.