Effects of methamphetamine on daily rhythms of hypothalamic norepinephrine, serotonin and plasma corticosterone levels in the rat

The relationship between daily rhythms of hypothalamic norepinephrine (NE) and serotonin (5HT) contents and the circadian rhythm of plasma corticosterone (Comp. B) levels was studied in the rat. It was found that levels of hypothalamic NE, 5HT and plasma Comp. B exhibited distinct daily flucturations in the control condition. In animals treated with methamphetamine, the daily rhythms of hypothalamic 5HT contents and plasma Comp. B levels remained unchanged, whereas the daily rhythm of hypothalamic NE contents was completely abolished. As a result, it was suggested that the daily rhythm of hypothalamic NE is not functionally related to the circadian change of pituitary-adrenocortical activity.     

Daily rhythm of plasma corticosterone binding activity in the white-throated sparrow,Zonotrichiaalbicollis

There is a bimodal daily rhythm of plasma corticosterone binding activity (CBA) in the white-throated sparrow, $\text{Zonotrichia}$$\text{albicollis}$, in the spring migratory condition. Low levels occurred at the beginning (0500) and at the end (2100) of a 16-hour daily photoperiod. Peak CBA occurred at 0900 and 0100, as did peak locomotor activity in this nocturnal migrant. Comparisons of CBA with total plasma corticosteroid concentrations from a previous study of the same group of birds indicate a positive correlation during most of the day but not during the early hours of darkness. The daily rhythm of locomotor activity may account for the rhythm of CBA which, in turn, may be partially responsible for the daily rhythm of plasma corticosteroid concentration.     

Effects of L-serine supplementation on the daily rhythms of growth hormone and corticosterone concentrations in mice

The impact of L-serine on the daily rhythms of growth hormone (GH) and corticosterone remains unknown. We explored whether the daily rhythms of these hormones were affected by L-serine supplementation as well as the supplementation time. The results showed that plasma GH concentration at Zeitgeber time (ZT)4 and 8 were significantly increased by L-serine supplementation at ZT22, while the diurnal rhythms peaks of plasma corticosterone at ZT12 were suppressed by L-serine supplementation at ZT10. After the supplementation was stopped, the effects of L-serine on the diurnal rhythms of plasma GH and corticosterone lasted for 2 days then they were fading on day 4. L-serine concentrations in plasma and hypothalamus after supplementation at ZT22 was lower than those after supplementation at ZT10. In conclusion, L-serine modulates the daily rhythms of GH and corticosterone depending on its supplementation time. The modulation effect might be association with the daily rhythms of L-serine metabolism.     

Changes in the daily rhythm of plasma corticosterone concentration related to seasonal conditions in the white-throated sparrow, Zonotrichia albicollis.

Circadian variations in concentrations of plasma corticosterone were investigated in the white-throated sparrow maintained on short (10-hr) or long (16-hr) daily photoperiods. In addition, the plasma concentrations of corticosterone were determined throughout a day in birds that were in the reproductively photosensitive spring migratory condition, the reproductively photorefractory post nuptial molt condition, and the fall migratory condition. Distinct unimodal rhythms were found in photosensitive birds. The daily rise occurred 12 hr after the offset of light in birds kept on both the short and the long photoperiodic regimens. There was no discernible daily variation in photorefractory birds kept on a 16 hr daily photoperiod and there was a bimodal rhythm in the birds that were in the fall migratory condition. The results are consistent with an hypothesis that assigns an important role to the circadian rhythm of corticosteroid concentration in the photoperiodic mechanism controlling seasonal reproductive and migratory conditions in the white-throated sparrow.     

Features of ginseng saponin-induced corticosterone secretion.

Ginseng saponin administered intraperitoneally to rats induced a significant rise in plasma corticosterone, while it tended to increase plasma glucose and to decrease plasma immunoreactive insulin. Oral or intraperitoneal administration of ginseng saponin increased plasma corticosterone in unanesthetized, pentobarbital-anesthetized or alloxan-diabetes rats. The histamine-induced rise in plasma corticosterone was suppressed by pretreatment with diphenhydramine, whereas the ginseng-induced rise was not. Ginseng saponin decreased rectal temperature while it increased plasma corticosterone. Ginseng-induced corticosterone secretion was superimposed on the basal levels of plasma corticosterone due to fasting and circadian rhythm. Thus ginseng saponin would be a kind of stressful agent and have different features associated with the stimulation of the pituitary-adrenocortical system from several other chemical agents.     

Development of Adrenocortical Cyclic Nucleotide (Cyclic AMP and Cyclic GMP) and Corticosterone Orcadian Rhythms in Male and Female Rats

The daily rhythm of the adrenocortical cyclic nucleotides (cyclic AMP and cyclic GIMP) was studied in infant male and female Wistar rats before and after the establishment of an adult-like daily rhythm of plasma corticosterone. As in this strain the rhythm of corticosterone is known to be present on postnatal day 18, pups of 2 and 3 weeks of age were studied. The dams and the pups as well as the young adult animals were kept on a controlled 12L-12D photoperiod. Groups of 8-10 pups were killed at 4-hr intervals throughout the day. Plasma corticosterone levels and adrenal cyclic AMP and cyclic GMP concentrations were simultaneously measured and the daily patterns established. Pups of 2 weeks of age showed neither plasma corticosterone nor adrenal cyclic AMP rhythms whereas pups of 3 weeks of age exhibited a typical adult-like circadian rhythm for both variables. The patterns for adrenal cyclic GMP differed according to sex: In female pups no cyclic GMP circadian rhythm could be detected at either 2 or 3 wk. In male pups of 3 wk a typical mature rhythm for adrenal cyclic GMP was evident whereas in younger male pups (2 wk) a circadian rhythm was detected. This circadian rhythm, however, differed from mature circadian rhythm in that its peak was located at 1300 hr instead of 0700 hr. These results demonstrate that, unlike that of cyclic AMP the adrenal cyclic GMP circadian rhythm does not appear at the same time as the plasma corticosterone circadian rhythm. Moreover, a circadian rhythmicity for adrenal cyclic GMP can be found in the absence of any corticosterone circadian rhythm. These facts argue against the view of cyclic GMP being a mediator of ACTH-stimulated steroidogenesis.     

Development of Adrenocortical Cyclic Nucleotide (Cyclic AMP and Cyclic GMP) and Corticosterone Orcadian Rhythms in Male and Female Rats

The daily rhythm of the adrenocortical cyclic nucleotides (cyclic AMP and cyclic GIMP) was studied in infant male and female Wistar rats before and after the establishment of an adult-like daily rhythm of plasma corticosterone. As in this strain the rhythm of corticosterone is known to be present on postnatal day 18, pups of 2 and 3 weeks of age were studied. The dams and the pups as well as the young adult animals were kept on a controlled 12L-12D photoperiod. Groups of 8–10 pups were killed at 4-hr intervals throughout the day. Plasma corticosterone levels and adrenal cyclic AMP and cyclic GMP concentrations were simultaneously measured and the daily patterns established. Pups of 2 weeks of age showed neither plasma corticosterone nor adrenal cyclic AMP rhythms whereas pups of 3 weeks of age exhibited a typical adult-like circadian rhythm for both variables. The patterns for adrenal cyclic GMP differed according to sex: In female pups no cyclic GMP circadian rhythm could be detected at either 2 or 3 wk. In male pups of 3 wk a typical mature rhythm for adrenal cyclic GMP was evident whereas in younger male pups (2 wk) a circadian rhythm was detected. This circadian rhythm, however, differed from mature circadian rhythm in that its peak was located at 1300 hr instead of 0700 hr. These results demonstrate that, unlike that of cyclic AMP the adrenal cyclic GMP circadian rhythm does not appear at the same time as the plasma corticosterone circadian rhythm. Moreover, a circadian rhythmicity for adrenal cyclic GMP can be found in the absence of any corticosterone circadian rhythm. These facts argue against the view of cyclic GMP being a mediator of ACTH-stimulated steroidogenesis.     

Adrenal splanchnic innervation contributes to the diurnal rhythm of plasma corticosterone in rats by modulating adrenal sensitivity to ACTH

Activity of the hypothalamic-pituitary-adrenal axis is characterized by a diurnal rhythm with an AM nadir and PM peak. Splanchnic nerve transection disrupts the diurnal rhythm in plasma corticosterone; however, there is a controversy as to whether the nerve-mediated effect is 1) via inhibition in the AM vs. excitation in the PM, or 2) involves changes in adrenal sensitivity to ACTH. The present studies were designed to address these issues. Adult male rats were anesthetized and underwent bilateral transection of the thoracic splanchnic nerve or sham transection. One week after surgery, rats were killed in the AM or PM with collection of nonstress plasma for measurement of corticosterone and ACTH. Plasma corticosterone was increased in the PM relative to the AM; however, plasma corticosterone in the PM was attenuated by splanchnic nerve transection, without affecting plasma ACTH. This decrease in PM plasma corticosterone after nerve-transection was 1) associated with decreased adrenal responsivity to ACTH, 2) associated with decreased adrenal cAMP content, 3) prevented by adrenal demedullation, and 4) not affected by removal of adrenal capsaicin-sensitive afferent fibers. Repeated serial blood sampling from individual rats confirmed the excitatory effect of splanchnic innervation in the PM. These results support the hypothesis that the adrenal splanchnic innervation modulates the diurnal rhythm in plasma corticosterone by increasing adrenal responsivity to ACTH and augmenting steroidogenesis in the PM and suggest that alterations in adrenal corticosterone secretion obscured by pulsatile secretion are more clearly revealed with repeated serial blood sampling.     

Daily and photoperiod variations of basal and stress-induced corticosterone concentrations in house sparrows (Passer domesticus)

Corticosterone concentrations were measured in captive house sparrows (Passer domesticus) and found to vary both daily and with different photoperiods. Basal corticosterone was highest during the dark hours of the daily cycle and lowest during the light hours. This trend remained constant when the birds were held on short-day and long-day light cycles, and while the birds were undergoing a prebasic molt. At all times, corticosterone concentrations significantly increased in response to the stress of handling and restraint. Stress-induced corticosterone concentrations, however, only reflected a daily rhythm when the birds were held on short-days. Furthermore, even though mean basal corticosterone concentrations were equivalent over the short-day, long-day, and molt, total corticosterone output in response to stress was lower in molting birds, especially at night. Therefore, these data indicate that captive house sparrows modulate corticosterone in daily cycles that change in response to photoperiod.     

Differential involvement of the suprachiasmatic nucleus in lipopolysaccharide-induced plasma glucose and corticosterone responses

The hypothalamic suprachiasmatic nucleus (SCN) is an essential component of the circadian timing system, and an important determinant of neuroendocrine and metabolic regulation. Recent data indicate a modulatory role for the immune system on the circadian timing system. The authors investigated how the circadian timing system affects the hypothalamo-pituitary-adrenal (HPA) axis and glucose regulatory responses evoked by an immune challenge induced by lipopolysaccharide (LPS). LPS-induced increases in corticosterone were minimal during the trough of the daily corticosterone rhythm; in contrast, LPS effects on glucose, glucagon, and insulin did not vary across time-of-day. Complete ablation of the SCN resulted in increased corticosterone responses but did not affect LPS-induced hyperglycemia. The paraventricular nucleus (PVN) of the hypothalamus is an important neuroendocrine and autonomic output pathway for hypothalamic information, as well as one of the main target areas of the SCN. Silencing the neuronal activity in the PVN did not affect the LPS-induced corticosterone surge and only slightly delayed the LPS-induced plasma glucose and glucagon responses. Finally, surgical interruption of the neuronal connection between hypothalamus and liver did not affect the corticosterone response but slightly delayed the LPS-induced glucose response. Together, these data support the previously proposed circadian modulation of LPS-induced neuroendocrine responses, but they are at variance with the suggested major role for the hypothalamic pacemaker on the autonomic output of the hypothalamus, as reflected by the effects of LPS on glucose homeostasis. The latter effects are more likely due to direct interactions of LPS with peripheral tissues, such as the liver.     

Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone

AimChronic consumption of a high-fat (HF) diet contributes to peripheral insulin resistance and elevated plasma corticosterone. However, the effect of HF consumption on the neurofunctional insulin receptors and neuronal corticosterone level is unclear. We tested the hypothesis that HF consumption can lead to peripheral insulin resistance, elevated neuronal corticosterone, and impaired neuronal responses to insulin.Main methodsMale Wistar rats were fed with normal diet or HF diet for 4, 8 or 12 weeks. At the end of each dietary period, plasma was collected for investigating peripheral insulin resistance parameters and corticosterone. Brains were then rapidly removed for studying the function of neuronal insulin receptors (IRs) by extracellular recording in CA1 hippocampus, neuronal IR signaling by immunoblot technique and neuronal corticosterone.Key findingsElevated plasma corticosterone level was initially seen in 4-week HF-fed rats. Peripheral insulin resistance developed at 8-week HF-fed rats. However, the elevated neuronal corticosterone level was found at 12-week HF consumption. The neuronal IR response demonstrated by insulin-mediated long-term depression in CA1 hippocampus was diminished in 12-week HF-fed rats. The phosphorylation levels of neuronal IR, IR substrate 1 and Akt/PKB were decreased in 12-week HF-fed rats with no change in these proteins. There was a correlation among peripheral insulin resistance, neuronal stress (elevated neuronal corticosterone), and neuronal insulin resistance in HF group.SignificanceOur findings suggest that HF consumption can lead to the elevation of corticosterone and peripheral insulin resistance, which could contribute to neuronal insulin resistance and neuronal stress.     

Thyroid hormones are required for daily rhythms of plasma corticosterone and prolactin concentration

Daily patterns of plasma corticosterone (B) and prolactin (PRL) concentration were measured in female rats which were intact (INTACT), thyroidectomized (THYREX), or thyroidectomized and given thyroxine (T₄) replacement (THYREX + T₄) (20 μg T₄/day). Bimodal daily rhythms of plasma B were present in INTACT rats and THYREX + T₄ rats. However, no plasma B rhythm was detectable in THYREX rats. THYREX + T₄ rats, which had greater mean T₄ concentrations than INTACT rats (6.0 μg/dl vs. 3.5 μg/dl), had a plasma B rhythm of greater amplitude than INTACT rats. Plasma PRL rhythms were detectable in INTACT and THYREX + T₄ rats, but not in THYREX rats. INTACT rats had a single peak in plasma PRL, whereas three plasma PRL peaks were present in THYREX + T₄ rats. It was concluded that thyroid hormones are required for the expression of plasma B and PRL rhythms and that the levels of thyroid hormones can alter the amplitude of the B rhythm and the shape of the PRL rhythm.     

Circadian rhythm of corticosterone in diabetic rats

We proposed that the circadian rhythm of corticosterone in diabetic rats would have a different pattern than that in non-diabetic control rats. To test this hypothesis, 20 male Sprague-Dawley rats were given ad libitum access to a stock diet and housed individually in a light and temperature controlled room. Ten rats were made diabetic by two subcutaneous injections of streptozotocin. Ten rats which were not injected served as controls. Thirteen days after induction of the diabetes, tail blood samples were taken every 4 h for 24 h. Plasma corticosterone levels were significantly higher in diabetic rats than in control rats at 3 time points during the light cycle; however, concentrations were similar during the dark cycle. We speculate that diabetes may cause alterations in the steroid feedback mechanism to the hypothalamus and/or pituitary, resulting in an abnormal circadian rhythm of plasma corticosterone.     

Forced Desynchrony Reveals Independent Contributions of Suprachiasmatic Oscillators to the Daily Plasma Corticosterone Rhythm in Male Rats

The suprachiasmatic nucleus (SCN) is required for the daily rhythm of plasma glucocorticoids; however, the independent contributions from oscillators within the different subregions of the SCN to the glucocorticoid rhythm remain unclear. Here, we use genetically and neurologically intact, forced desynchronized rats to test the hypothesis that the daily rhythm of the glucocorticoid, corticosterone, is regulated by both light responsive and light-dissociated circadian oscillators in the ventrolateral (vl-) and dorsomedial (dm-) SCN, respectively. We show that when the vlSCN and dmSCN are in maximum phase misalignment, the peak of the plasma corticosterone rhythm is shifted and the amplitude reduced; whereas, the peak of the plasma adrenocorticotropic hormone (ACTH) rhythm is also reduced, the phase is dissociated from that of the corticosterone rhythm. These data support previous studies suggesting an ACTH-independent pathway contributes to the corticosterone rhythm. To determine if either SCN subregion independently regulates corticosterone through the sympathetic nervous system, we compared unilateral adrenalectomized, desynchronized rats that had undergone either transection of the thoracic splanchnic nerve or sham transection to the remaining adrenal. Splanchnicectomy reduced and phase advanced the peak of both the corticosterone and ACTH rhythms. These data suggest that both the vlSCN and dmSCN contribute to the corticosterone rhythm by both reducing plasma ACTH and differentially regulating plasma corticosterone through an ACTH- and sympathetic nervous system-independent pathway.     

The effect of transdermal corticosterone application on plasma corticosterone levels in pregnant Lacerta vivipara

Relationships between hormones and behaviour can be explored by altering endogenous hormone levels, often through implantation of silastic tubing or osmotic pumps filled with a hormone or its agonists or antagonists. However, organisms in sensitive life-history stages (such as pregnancy) may be adversely affected by the surgical procedures associated with these manipulations, necessitating use of non-invasive techniques. We demonstrate that the application of a sesame oil-corticosterone mixture to the skin of pregnant female common lizards (Lacerta vivipara) elevates plasma levels of the hormone. Pregnant female L. vivipara were captured and treated daily for 1-20 days with the sesame oil-corticosterone mixture (experimental group) or with vehicle only (control group). Blood samples were collected and analyzed for corticosterone by radioimmunoassay. Baseline plasma corticosterone levels were elevated within 1 h in the experimental group. Similar levels ( approximately 145 ng/ml) were found over the subsequent 2 days, and by day 5 had risen significantly higher ( approximately 281.9 ng/ml), where they remained for the duration of the experiment. These increases are comparable to those found in other species using related techniques. No significant changes in plasma corticosterone levels occurred in the control group. Finally, corticosterone levels also were determined for untreated females that were captured, held overnight, sampled, and released to access to the natural range of basal corticosterone levels. Basal plasma levels of corticosterone in pregnant females varied among individuals independently of female body size or corpulence.     

High-performance liquid chromatographic separation of corticosteroids in plasma of rats. Its application to the determination of the circadian rhythm of 18-hydroxycorticosterone related to aldosterone and corticosterone

An efficient separation of corticosteroids in plasma of rats was obtained by reversed-phase high-performance liquid chromatography (HPLC). Plasma corticosteroid assays with HPLC separation were used to determine the circadian rhythm of 18-hydroxycorticosterone (18-OHB) and its possible relationship to aldosterone or corticosterone in conscious rats under standard conditions (regular diet; 12-hour light and 12-hour dark cycle). Significant circadian rhythms of plasma corticosterone, 18-OHB and aldosterone were observed with peak values at 20.00 h and nadir values at 08.00 h. The mean ratio of plasma 18-OHB to aldosterone during 24 h was 2.4. The circadian rhythm of 18-OHB was also correlated with that of plasma aldosterone or corticosterone.     

Effects of time of l-ornithine administration on the diurnal rhythms of plasma growth hormone,melatonin, and corticosterone levels in mice

The synthesis and secretion of many hormones such as growth hormone (GH), melatonin, and corticosterone, exhibit temporal variations over each day and night. Oral administration of several nutritional factors, including l-ornithine, modulates these hormonal secretions and induces an acute increase in plasma GH levels. However, the impact of l-ornithine on the diurnal rhythms of hormone secretion remains unclear. In this study, we evaluated whether the diurnal rhythms of plasma GH, melatonin, and corticosterone secretion were altered by the daily administration of l-ornithine as well as the timing of the administration, in CBA/N mice. Our results showed that the plasma GH levels that peaked at light phase were amplified by l-ornithine (500?mg/kg) administered at Zeitgeber time (ZT) 22, but not at ZT10. Additionally, l-ornithine (1000?mg/kg) administered at ZT22 advanced the onset of the nocturnal rise of melatonin, which resulted in the elongation of the melatonin peak. On the other hand, l-ornithine (500 and 1000?mg/kg) administered at ZT10, but not at ZT22, suppressed the diurnal rhythm peaks of plasma corticosterone. The effects of l-ornithine on plasma GH rhythms lasted for at least 2 days after cessation of the daily administration. Running wheel activity during the active phase was slightly elevated by l-ornithine administration at ZT22, but the overall patterns were only slightly affected. l-Ornithine levels in the plasma and hypophysis after a single administration of l-ornithine at ZT22 were lower than those after administration at ZT10, suggesting that the metabolic rate of l-ornithine differs between day and night. In conclusion, our data suggest that a daily administration of l-ornithine regulates the diurnal rhythms of GH, melatonin, and corticosterone in a manner dependent on administration time, which might be related to the diurnal rhythms of l-ornithine metabolism.     

Plasma corticosterone in chicks reared under several lighting schedules

Plasma corticosterone was determined by radioimmunoassay in 6-7-week-old male broiler type chicks, reared under several carefully controlled lighting regimes. When subjects were grouped by photoperiod of rearing, chicks reared in darkness had significantly lower hormone levels than diurnal controls, or than subjects reared in continuous light. Around-the-clock sampling revealed a diurnal corticosterone rhythm, with high daytime levels and lower night-time levels. This rhythm appeared to be retained in constant light, although phase shifted or free running. Neither analysis by light intensity level nor by lights on/lights off status at the time of blood sampling revealed differences in plasma corticosterone between the experimental groups which could be attributed to these factors.     

Attenuated blood corticosterone rhythm in rats with jejunal resection

Circadian rhythmic changes in blood corticosterone concentration were studied in rats after resection of the jejunum or the ileum. The rats with ideal resection showed a normal corticosterone rhythm, with a peak at the beginning of the dark period when they were fed ad libitum, and the phase of the rhythm shifted when the feeding time was restricted to a specific time of day during the light period. The rats with jejunal resection also showed a similar corticosterone rhythm, but its amplitude was lower compared to that of the rats with ideal resection. There were no differences in body weight and the circadian rhythm of blood urea concentration between two groups of rats. We conclude that the jejunum is an important site where the sense of food is received as an entraining signal for the corticosterone rhythm.     

Influence of the corticosterone rhythm on photic entrainment of locomotor activity in rats

The question of involvement of glucocorticoid hormones as temporal signals for the synchronization of the timekeeping system was addressed in rats with different corticosterone status. The authors showed that adrenalectomy had no effects on the synchronization of wheel-running activity rhythms to a steady-state LD 12:12 cycle, regardless of whether it was compensated for by a corticosterone replacement therapy that either reinstated constant plasma concentrations of the hormone or mimicked its natural rhythm. However, after a 12-h phase shift (daylight reversal), the lack of circulating corticosterone induced a significant shortening of the resynchronization rate (less than 3 days vs. 7 days). Normalization required restoration of a rhythmic corticosterone secretion that was synchronized to the new photoperiod. Under constant darkness, the corticosterone rhythm did not show any synchronizing effect, providing evidence that it participates in entrainment of the locomotor activity rhythm through modulation of light effects. It is proposed that, under stable lighting conditions, circulating glucocorticoids contribute to stabilizing activity rhythms by reinforcing resistance of the circadian timing system to variations of the photoperiod. Experimental evidence that serotonergic neurons are involved in relaying their modulatory effects to the clock is also presented.