EFFECTS OF LESIONS OF THE SUPRACHIASMATIC NUCLEI AND OF p-CHLOROPHENYLALANINE ON THE CIRCADIAN RHYTHMS OF ADRENOCORTICOTROPHIC HORMONE AND CORTICOSTERONE IN THE PLASMA, AND ON LOCOMOTOR ACTIVITY OF RATS

Abstract

Adrenocorticotrophin (ACTH) and corticosterone in the plasma of adult female rats were measured sequentially at 4 h intervals for 24 h before and after lesions of the suprachiasmatic nuclei or treatment with p-chlorophenylalanine (to inhibit serotonin synthesis). After lesions or p-chlorophenylalanine treatment, the concentrations of ACTH were diminished relative to those in control animals and rhythmic changes could not be detected. However, injection of animals, pretreated with p-chlorophenylalanine, with 5-hydroxytryptophan (60 mg/kg) 8 h before the time when plasma ACTH is maximal in intact animals, stimulated ACTH secretion up to control values. Mean corticosterone concentrations in plasma remained unchanged (after lesions) or increased (after p-chlorophenylalanine). This increase was associated with an increased minimal concentration of corticosterone. After both treatments there was evidence of continued circadian or ultradian rhythms of corticosterone concentration. Locomotor activity of female rats given identical treatment, but without blood sampling, indicated that nocturnal activity was diminished after lesions whereas diurnal activity was enhanced after p-chlorophenylalanine treatment. Periodicity analysis detected the persistence of free-running circadian, and sometimes ultradian activity, rhythms. Adrenalectomy did not alter further the activity pattern observed in rats with lesions. These results therefore support the proposition that both the suprachiasmatic nuclei and the serotoninergic system play an irreplaceable role in the mechanism of ACTH secretory rhythms. The suprachiasmatic nuclei are also important for synchronization of locomotor activity and corticosterone rhythms, which may both persist after the suppression of ACTH rhythms.

Glucocorticoids and the circadian clock

“…The circadian aspects of the rhythmic release of glucocorticoids and their tropic hormone ACTH are under control of the SCN, since SCN lesions abolish the rhythms (Moore & Eichler 1972, Abe et al 1979, Szafarczyk et al 1979, Cascio et al 1987. Interestingly, the SCN also exhibits ultradian rhythms of activity, but at present it is unknown if and how these rhythms might contribute to the ultradian rhythms of the HPA axis and of glucocorticoid release (Yamazaki et al 1998, Lowry 2002.…”

Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

“…This corresponds to the light phase of a light/dark (LD) cycle for humans, and the dark phase of the LD cycle for rats and mice (3,4). Under conditions of constant darkness, circadian rhythms in locomotor behavior and HPA axis function persist, reflecting the function of an endogenous clock mechanism (5)(6)(7). This central nervous system pacemaker requires an intact suprachiasmatic nucleus (SCN), since animals with SCN lesions lose rhythmicity of locomotor, adrenocortical, and sleep-wake modulation (8,9).…”

A Diurnal Rhythm of Stimulatory Input to the Hypothalamo–Pituitary–Adrenal System as Revealed by Timed Intrahypothalamic Administration of the Vasopressin V1Antagonist

“…The main force driving the endogenous circadian rhythm of basal HPA activity is the suprachiasmatic nucleus (SCN) in the anterior hypothalamus (Moore and Eichler, 1972;Abe et al, 1979;Szafarczyk et al, 1979;Cascio et al, 1987). In a number of previous studies, we provided evidence for an important inhibitory role of SCN-derived vasopressin (VP) with respect to the basal release of corticosterone.…”