Effects Of Corticosterone Administration Research Articles

Ceftriaxone modulates the acute corticosterone effects in local field potentials in the primary somatosensory cortex of anesthetized mice

Stress responses are associated with elevations in corticosterone levels and, as a consequence, increases in glutamate in the central nervous system which can lead to neurological impairment. Ceftriaxone promotes glutamate transport and has been used to reduce glutamate toxicity, but so far it is not known whether ceftriaxone is able to reverse the effects of corticosterone administration. Here we describe the separate and combined effects of acute ceftriaxone and acute corticosterone administration in local field potentials (LFPs) recorded from the somatosensory cortex (S1) of anesthetized mice. For this, LFPs were recorded from groups of anesthetized mice injected with saline, corticosterone, ceftriaxone, or both. Comparison of global state maps, and their displacements, as measured by ratios of different frequency bands (Ratio 1: 0.5–20 Hz/0.5–45 Hz; and Ratio 2: 0.5–4.5 Hz/0.5–9 Hz) revealed distinct and opposite effects for corticosterone and for ceftriaxone. Corticosterone specifically increased the displacement in Ratio 2, while ceftriaxone decreased it; in addition, when both corticosterone and ceftriaxone were injected, Ratio 2 displacement values were again similar to those of the control group. The present results suggest that ceftriaxone and corticosterone modulate specific frequency bands in opposite directions and reveal a potential role for ceftriaxone in counteracting the effects of corticosterone.

Chronic corticosterone-induced depression mediates premature aging in rats

BackgroundStress hormones such as corticosterone (CORT) play an essential role in the development of depression. Chronic CORT administration has been shown to induce dysfunction in the hypothalamic–pituitary–adrenal axis leading to depression, which was in turn associated with accelerated aging. However, the effect of CORT administration on aging remains unclear. MethodsRats were acclimatized for 1 week and then injected daily with CORT (40mg/kg) or vehicle (n = 10 each) for 21 consecutive days. Age-related indexes were then compared between CORT-treated rats and control rats. ResultsCORT induced affective behaviors indicative of depressive-like symptoms in rats, including reduced sucrose preference and increased immobility time in the forced swimming test. CORT-treated rats exhibited telomere shortening, possibly contributing to decreased telomerase activity and down-regulated expression of telomere-binding factor 2, correlated with enhanced oxidative damage. This was associated with inhibition of sirtuin 3 leading to reduced activities of superoxide dismutase 2 and glutathione reductase. CORT-treated rats showed degenerated mitochondrial functions represented by decreased adenosine triphosphate production, decreased nicotinamide adenine dinucleotide+ content, and decreased activity of nicotinamide phosphoribosyltransferase. LimitationsThe group sample sizes were small, and only male rats and a single dose level of CORT were used. ConclusionThese findings demonstrate that CORT-induced depression may be involved in mediating the pathophysiology of premature aging in rats.

GABAergic control of the activity of the central nucleus of the amygdala in low- and high-anxiety rats

The aim of this study was to examine the role of GABAergic neurotransmission in amygdala nuclei in low- (LR) and high-anxiety (HR) rats after repeated corticosterone administration and acute injection of the benzodiazepine midazolam. The animals were divided into LR and HR groups based on the duration of their conditioned freezing in a contextual fear test (CFT). Repeated daily administration of corticosterone (20 mg/kg s.c.) for 21 injections increased anxiety-like behavior in the open field and reduced body weight in both the LR and HR groups. These effects of corticosterone administration were more pronounced in the HR group. Moreover, in the HR group, chronic corticosterone administration increased the duration of freezing in the CFT test compared with the appropriate control group and treated LR rats. The behavioral effects in HR rats were accompanied by an increase in the expression of c-Fos in the lateral (LA) and central (CeA) nuclei of the amygdala and by a decrease in GABA-A alpha-2 subunit density in the CeA. Acute midazolam administration significantly attenuated the neophobia and conditioned fear responses, decreased c-Fos expression in the LA and CeA, and increased alpha-2 subunit density in the CeA only in the HR group. These studies have shown that HR rats are more susceptible to the anxiogenic effects of chronic corticosterone administration, which are associated with the attenuation of GABAergic control over the amygdala output that controls emotional responses. The current data may increase understanding of the neurobiological mechanisms responsible for individual differences in the psychopathological processes induced by repeated administration of high doses of glucocorticoids or by elevated levels of these hormones, which are associated with chronic stress and affective pathology.

The effect of chronic administration of corticosterone on anxiety- and depression-like behavior and the expression of GABA-A receptor alpha-2 subunits in brain structures of low- and high-anxiety rats

The aim of this study was to examine changes in rat emotional behavior and determine differences in the expression of GABA-A receptor alpha-2 subunits in brain structures of low- (LR) and high-anxiety (HR) rats after the repeated corticosterone administration. The animals were divided into LR and HR groups based on the duration of their conditioned freezing in a contextual fear test. Repeated daily administration of corticosterone (20mg/kg) for 21days decreased activity in a forced swim test, reduced body weight and decreased prefrontal cortex corticosterone concentration in both the LR and HR groups. These effects of corticosterone administration were stronger in the HR group in comparison with the appropriate control group, and compared to LR treated and LR control animals. Moreover, in the HR group, chronic corticosterone administration increased anxiety-like behavior in the open field and elevated plus maze tests. The behavioral effects in HR rats were accompanied by a decrease in alpha-2 subunit density in the medial prefrontal cortex (prelimbic cortex and frontal association cortex) and by an increase in the expression of alpha-2 subunits in the basolateral amygdala. These studies have shown that HR rats are more susceptible to anxiogenic and depressive effects of chronic corticosterone administration, which are associated with modification of GABA-A receptor function in the medial prefrontal cortex and basolateral amygdala. The current data may help to better understand the neurobiological mechanisms responsible for individual differences in changes in mood and emotions induced by repeated administration of high doses of glucocorticoids or by elevated levels of these hormones associated with chronic stress or affective pathology.

Imipramine counteracts corticosterone-induced enhancement of glutamatergic transmission and impairment of long-term potentiation in the rat frontal cortex

AbstractThe effects of corticosterone administration lasting for 7 and 21 days were studied ex vivo in rat frontal cortex slices prepared 48h after the last dose of the hormone. In slices originating from corticosterone-treated animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Corticosterone administration also resulted in an increase of the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These effects were accompanied by a reduced magnitude of long-term potentiation (LTP) of field potentials. In a separate set of experiments, rats were treated with corticosterone for 21 days and additionally with a tricyclic antidepressant, imipramine, beginning on the eighth day of corticosterone administration. In this experimental group, the amplitude of field potentials, the mean frequency of sEPSCs and the magnitude of LTP were not different from the control, indicating that corticosterone-induced modifications of basal glutamatergic transmission and synaptic plasticity were reversed by the antidepressant.

Effect of Corticosterone Administration on Small Intestinal Weight and Expression of Small Intestinal Nutrient Transporter mRNA of Broiler Chickens

The effects of corticosterone (CORT) administration on the weight of small intestine and the expression of nutrient transporter mRNA in the small intestine of broiler chickens (Gallus gallus domesticus) were investigated. One hundred and eight seven-day-old birds were randomly divided into two equal groups comprising a control group (CTRL) and an experimental group (CORT). CTRL birds were fed a basal diet and the CORT birds were fed a basal diet containing 30 mg corticosterone/kg from d 8 to 21. At 21 d of age, average daily feed intake (ADFI), serum corticosterone level, small intestinal absolute wet weight and relative weight, and relative abundance of SGLT1, CaBP-D28k, PepTl mRNA in the duodenum and L-FABP mRNA in the jejunum were determined. The results showed that serum corticosterone level, liver weight and small intestinal relative weight (small intestinal wet weight/body weight) of CORT chickens were about 30.15%, 26.72% and 42.20% higher, respectively, than in the CTRL group (p<0.05). CORT birds had relative mRNA abundance of CaBP-D28k and PepT1 in the duodenum, and L-FABP in the jejunum which was 1.77, 1.37 and 1.94 fold higher, respectively, than in the CTRL group (p<0.05); the relative abundance of SGLT1 was 1.67 fold higher than in the CTRL group (p = 0.097). ADFI, small intestinal wet weight and length in CORT-treated broiler chickens was about 29.11%, 31.12% and 12.35% lower, respectively, than in the CTRL group (p<0.05). In conclusion, corticosterone administration lowered the wet weight but increased the relative weight of the small intestine and the expression of intestinal nutrient transporter mRNA of broiler chickens.

Corticosterone Alters Meat Quality by Changing Pre-and Postslaughter Muscle Metabolism

Two experiments were conducted to investigate the effect of acute preslaughter stress mimicked by exogenous corticosterone (CORT) administration on postmortem muscle metabolism of broiler chickens. Altered protein metabolism, glycogen depletion, and meat quality characteristics were investigated in the musculus pectoralis major (PM) and musculus biceps femoris of broiler chickens. Results showed that CORT administration resulted in increased proteolysis and gluconeogenesis, whereas the capacity for protein synthesis was not obviously changed. Plasma levels of glucose, urate, and total free amino acids were all significantly decreased by CORT treatment. The effect of CORT administration on muscle R-values remained uncertain. The initial muscle buffer capacity was increased by CORT treatment in both musculus pectoralis major and musculus biceps femoris. The results suggested that the acute premortem up-regulation of CORT decreased muscle ultimate pH by increasing the antemortem muscle glycogen content and its depletion rate postmortem, which in turn induced a decrease in water-holding capacity. Muscle buffering capacity might be altered by CORT administration, and its involvement in the change of muscle pH needs to be investigated further.

Effect of corticosterone administration on mammary gland development and p27 expression and their relationship to the effects of energy restriction on mammary carcinogenesis.

The inhibitory activity against mammary carcinogenesis mediated by energy restriction is accompanied by a reduction in the degree of mammary ductal branching, and an increase in adrenal cortical activity. Levels of p27/kip1 protein, a gene product associated with cell cycle growth arrest, have also been shown to be elevated in mammary epithelium and in mammary lesions of energy-restricted animals. Based on these data we have proposed that increased secretion of adrenal cortical steroids accounts, in part, for the effects of energy restriction. In this experiment the hypothesis tested was that corticosterone administration would mimic the effects of energy restriction, both on mammary gland development and on levels of p27 protein in mammary ductal epithelium. To test this hypothesis corticosterone was fed to female rats for 4 weeks. Dietary corticosterone increased serum and urinary corticosterone levels in a dose-dependent manner (P < 0.01). The effects of corticosterone treatment on mammary gland development were analyzed digitally; p27 protein was detected immunohistochemically. The ductal extension and branching of the mammary gland were reduced in a dose-dependent manner by corticosterone treatment (P < 0.05); however, the magnitude of the effect was greater on ductal branching. Overall, increasing dietary corticosterone reduced the total volume of mammary epithelium in a dose-dependent manner, an effect that remained even after adjustments for differences among animals in body mass. Consistent with this effect, the amount of p27 protein present in ductal mammary epithelial cells increased dose-dependently in response to increasing corticosterone administration (P < 0.01). The hypothesis is proposed that dietary administration of corticosterone may imitate the effects of energy restriction on mammary carcinogenesis by regulation of mammary tissue size homeostasis via p27/kip1 mediated arrest of cell cycle progression.

Effects of corticosterone administration on local cerebral glucose utilization of rats

The local cerebral glucose utilization (LCGU) of control and 2 day corticosterone-administered rats was investigated using the method of Sokoloff (labelled 2-deoxy- d-glucose). The overall LCGU of both groups was similar, but discrete areas of the corticosterone-administered rat brains displayed both increases and decreases in their utilization of 2-deoxyglucose. These areas were associated with limbic cortex and included the hippocampus, the septum and some thalamic and hypothalamic nuclei. It is well known that these regions are interconnected and that acetylcholine is one of the main neurotransmitters. Some of these pathways (as measured electrophysiologically) have reportedly inhibitory influences, whilst others have excitatory ones within the limbic region. It was therefore striking to observe that these inhibitory or stimulatory effects were corroborated by a selective, corticosterone-induced decrease or increase in 2-deoxyglucose uptake, respectively. This gives corticosterone a putative role in the regulation of the limbic system. As the latter has been reported to be abnormal in genetically obese hypercorticosteronemic fa/ fa rats, it is suggested that these corticosterone-induced changes within the limbic system may contribute to the overall phenotypic expression of this obesity state.

Effects of corticosterone administration on nitrogen excretion and nitrogen balance in adrenalectomized rats

Adrenalectomized rats were implanted with pellets containing corticosterone in proportions varying from 0% to 100%, plus cholesterol. Stable concentrations of plasma corticosterone resulted, varying from subnormal (A) to physiologic (B) to supraphysiologic (C). When food was ingested ad libitum, weight gain was maximal in B at plasma corticosterone concentrations of 0.14-0.20 mumol/L; weight loss occurred in C, despite higher food intake. Even when rats had constant limited food intake, weight gain and positive nitrogen balance were significantly reduced in A compared with B because fecal nitrogen rose significantly and the retention of absorbed nitrogen for growth decreased. In C, weight decreased despite constant intake, and nitrogen balance became negative because urinary nitrogen increased markedly. We conclude that glucocorticoid insufficiency reduces nitrogen balance by impairing intestinal absorption of dietary protein and the utilization of absorbed nitrogen, whereas glucocorticoid excess reduces nitrogen balance by augmenting urinary nitrogen despite constant nitrogen intake.

Pituitary-adrenal and dopaminergic modulation of schedule-induced polydipsia: behavioral and neurochemical evidence.

Five experiments investigated in rats the effects of increasing or decreasing plasma corticosterone levels on schedule-induced polydipsia and dopamine efflux in the nucleus accumbens. The results indicate that the acquisition of schedule-induced polydipsia could be decreased by adrenalectomy, blockade of corticosterone synthesis, or administration of corticosterone. Performance of established schedule-induced polydipsia was also decreased by adrenalectomy. The effects of corticosterone administration on established schedule-induced polydipsia depended on the level of performance. High levels of drinking were enhanced by a high dose of corticosterone, whereas low rates of drinking were increased by a low dose. Similar injections of corticosterone also significantly increased dopamine efflux. The relative involvement of pituitary-adrenal activity and dopamine neurotransmission in the nucleus accumbens in the acquisition and performance of SIP is discussed and related to contemporary hypotheses of schedule-induced behavior.

Effect of corticosterone administration at varying levels on leucine oxidation and whole body protein synthesis and breakdown in adrenalectomized rats

Adrenalectomized rats were implanted with pellets containing corticosterone in proportions varying from 0% to 100%, plus cholesterol. Stable levels of plasma corticosterone resulted, varying from close to zero (I) to physiologic (II) to supraphysiologic (III). Whole body protein synthesis (S) was measured during fasting by a technique involving injection of [1- 14C]-leucine, analysis of expired air for 14CO 2, and measurement of urinary excretion of urea N plus ammonia N(C). Whole body breakdown (B) during fasting was calculated as the sum of S and C. C rose progressively from I to III, but fractional oxidation of 14C leucine was lowest in II. Both S and B were markedly reduced in I and maximal in II. In III, S fell but B remained high. Thus variations in glucocorticoid levels above and below physiologic exert profound effects on leucine oxidation and protein turnover, involving effects on both synthesis and breakdown.

The effects of renin and adrenalectomy on blood distribution and capillary permeability.

Capillary permeability following renin-angiotensin infusion and adrenalectomy in the rat was investigated in different areas of the circulation by studying the rate of disappearance from the circulation of radioactive albumin and, since it appeared particularly increased in the splanchnic bed, by studying the rate of excretion into the thoracic duct of intravenously injected fluorescein-labelled albumin. Studies on blood volume distribution with125I albumin in different organs and tissues and the direct measurement of blood flow in the splanchnic bed, demonstrated a significant corre­lation between the effect of adrenalectomy and of renin-angiotensin on capillary permeability and the haemodynamic changes which they cause. Possible ways by which adrenalectomy and renin-angiotensin infusion cause a redistribu­tion of blood flow and the effect of corticosterone administration in this respect, are also described.