Biomedical subjects

R R Sakai

Publications and source records attributed to R R Sakai.

At least 19 recordsLinked to original sources

PubMed2000

Chronic social stress reduces dendritic arbors in CA3 of hippocampus and decreases binding to serotonin transporter sites.

Male rats housed in mixed-sex groups in a visible burrow system (VBS) form a dominance hierarchy in which subordinate animals show stress-related changes in behavior, endocrine function and neurochemistry. Dominants also appear to be moderately stressed compared to controls, although these animals do not develop the more pronounced behavioral and physiological deficits seen in the subordinates. In the present study, we examined the effects of chronic psychosocial stress on the morphology of Golgi-impregnated CA3 pyramidal neurons. In addition, since serotonin has been implicated in the mechanisms mediating the dendritic remodeling seen with other chronic stress regimens, we used quantitative autoradiography to measure binding to the serotonin transporter (5HTT) in hippocampus and dorsal and median raphe. Chronic social stress led to a decrease in the number of branch points and total dendritic length in the apical dendritic trees of CA3 pyramidal neurons in dominant animals compared to unstressed controls; subordinates also had a decreased number of dendritic branch points. [(3)H]paroxetine binding to the 5HTT was decreased in Ammon's horn in both dominants and subordinates compared to controls, while 5HTT binding remained unchanged in dentate gyrus and raphe. The similarity of the changes in 5HTT binding and dendritic arborization between both groups of VBS animals, despite apparent differences in stressor severity, suggests that these changes may be part of the normal adaptive response to chronic social stress. The mechanisms underlying dendritic remodeling in CA3 pyramidal neurons are likely to involve stress-induced changes in glucocorticoids and in 5HT and other transmitters.

Animals↗

PubMed2000

The amygdala: site of genomic and nongenomic arousal of aldosterone-induced sodium intake.

UNLABELLED: BACKGROUND.: Mineralocorticoids act on the brain to influence sodium intake, and they do so via intracellular type I receptors and possibly also via a direct membrane action, as they do in the kidney. One brain area implicated by lesion studies investigating the regulation of sodium appetite aroused by adrenal steroids is the amygdala. METHODS: To examine the mechanism by which mineralocorticoids act in the amygdala to arouse salt intake via a genomic and or membrane mode of action, rats were bilaterally fitted with cannulae directed to terminate in the amygdala. The genomic action of mineralocorticoids in arousing sodium intake was investigated by the administration of antisense oligodeoxynucleotides (ASDNs) against the mineralocorticoid receptor, and its effects on deoxycorticosterone (DOCA)-induced sodium intake over the course of several days was examined. The nongenomic action of mineralocorticoids on sodium intake was investigated by implantation into the amygdala of DOCA, aldosterone (ALDO), or their A-ring-reduced tetrahydro derivatives, 15 minutes prior to access to saline. Sodium intake was monitored immediately thereafter. RESULTS: Treatment of rats in the amygdala with ASDN against the mineralocorticoid receptor inhibited DOCA-induced sodium intake, whereas ASDN against the glucocorticoid receptor or sense/scrambled sequences had no effect. DOCA and ALDO increased saline intake within 15 minutes after steroid application. Similarly, the application of A-ring-reduced 3beta,5beta tetrahydroaldosterone and 5 alpha-tetrahydrodeoxycorticosterone produced the same increases in sodium intake. CONCLUSIONS: Together, the data imply that adrenal steroids, in addition to acting through classic cytosolic receptors, may also act on membrane receptor systems, producing rapid changes in behavior.

Aldosterone↗

PubMed2000

Estrogen increases angiotensin II-induced c-Fos expression in the vasopressinergic neurons of the paraventricular nucleus in the female rat.

Previous studies in female rats have shown that estrogen treatment attenuates angiotensin II (AngII)-induced water intake. The mechanism underlying this attenuation may be decreased responsiveness to AngII, as revealed by a reduction in AngII binding to the angiotensin type 1 (AT1) receptor in the subfornical organ (SFO). It has not been determined whether these changes in receptor binding translate into changes in neuronal activity that, in turn, may influence behavior. Therefore, an estrogen-modulated change in neuronal pathways relevant to AngII-induced water intake was tested in ovariectomized (OVX) female rats using immunohistochemistry for the immediate early gene c-Fos as a marker for neuronal activation. Third cerebroventricular injection of AngII (6 ng) induced intense c-Fos immunoreactivity in forebrain regions associated with fluid intake, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus, the SFO, the supraoptic nucleus and the paraventricular nucleus (PVN). Forty-eight-hour estradiol (10 microg) administration to OVX female rats increased AngII-induced c-Fos labeling in the lateral magnocellular neurons of the PVN by 30% as compared to vehicle-treated controls. Double labeling neurons in the PVN with c-Fos and either vasopressin or oxytocin antisera revealed that estrogen increased AngII-induced c-Fos expression by 28%, specifically in vasopressinergic neurons. Such changes in neuronal activation may explain the estrogen modulation of AngII-induced water intake that has been previously reported; it may be due to increased water retention to maintain plasma osmolality or to induction of a pressor response.

Angiotensin II↗

PubMed1999

11beta-hydroxysteroid dehydrogenase functions reversibly as an oxidoreductase in the rat hippocampus in vivo.

The localization in the brain and metabolism of 3H-labeled corticosterone (B) and 11-dehydrocorticosterone (A) of high specific radioactivity was determined after stereotaxic injection into the hippocampus of anesthetized rats. [3H]B was cleared very rapidly with, on average, only about 7% being recovered after 5 min and 0.5% after 30 min. Most of this 3H-radioactivity was localized in the area surrounding the site of injection with little diffusion to adjacent areas. These findings make it possible to compare the short term metabolism of [3H]A and [3H]B in different lobes of the hippocampus in the same animal and establish their local equilibrium point in vivo. Under these conditions, about 5% conversion of each steroid to the other was observed in contrast to the situation in cultured hippocampal cells where 11beta-hydroxysteroid dehydrogenase (11-HSD) has been shown by others to act primarily as a reductase catalyzing the conversion of A to B. This method can also be used to study the effect of inhibitors such as 11alpha-hydroxyprogesterone, applied locally in the brain, on the metabolism of corticosteroids. The rate of conversion [3H]B or [3H]A to their dihydro- and tetrahydro-derivatives capable of modulating the GABAa receptor in the hippocampus was much lower than their interconversion. Thus, factors which influence the direction of the 11-HSD catalyzed reaction are important in regulating not only salt appetite and blood pressure but also the levels of neuroactive metabolites of corticosterone.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1999

The angiotensin AT(1) receptor antagonist irbesartan has near-peptide affinity and potently blocks receptor signaling.

The angiotensin II type 1 (AT(1)) receptor plays a pivotal role in the regulation of blood pressure and electrolyte balance, and is involved in the control of specific ingestive behaviours. Irbesartan (SR 47436/BMS 186295) is a recently developed angiotensin AT(1) receptor antagonist, chemically described as 2-butyl-3-([2'-¿1H-tetrazol-5-yl¿biphenyl-4-yl]methyl)-1, 3-diazaspiro (4,4)non-1-en-4-one. Irbesartan displays higher affinity for its target receptor than other similar antagonists. In radioligand binding assays performed on membranes from WB-Fischer 344 (WB) rat liver epithelial cells, irbesartan was able to displace [125I]angiotensin II with a K(i) of 4.05 nM as compared to losartan (DuP 753) and tasosartan (WAY 126756), which had K(i) values of 25.2 nM and 46.6 nM, respectively. Similarly, in functional assays, irbesartan exhibited the highest functional potency to block angiotensin II-induced inositol trisphosphate (IP(3)) turnover. The improved affinity of irbesartan for the angiotensin AT(1) receptor does not coincide with a concomitant increase in affinity for the angiotensin AT(2) receptor, as irbesartan and losartan exhibited the same low potency to displace [125I]angiotensin II in radioligand binding assays performed on membranes from PC-12w cells. In binding assays performed on peripheral tissues in rat, irbesartan bound to the angiotensin AT(1) receptor expressed in liver, adrenal, kidney and pituitary with an overall affinity closely approaching that of the high affinity peptidic antagonist [Sar(1), Ile(8)]angiotensin II. Due to the higher affinity of irbesartan over other similar antagonists for the angiotensin AT(1) receptor in many tissues and its greater potency to block receptor activation, irbesartan may be quite useful in the study of the angiotensin AT(1) receptor and its role in controlling ingestive behaviours and, furthermore, shows great potential to improve the treatment of hypertension and other cardiovascular disease states.

Adrenal Glands↗

PubMed1999

Estrogen decreases hypothalamic angiotensin II AT1 receptor binding and mRNA in the female rat.

Estrogen has been shown to modulate angiotensin II (AngII)-regulated behaviors, such as thirst, and may do so by influencing the central renin-angiotensin system (RAS). While numerous studies have attempted to correlate changes in AngII receptors or other components of the RAS with estrogen treatment, the low abundance of these genes has made comparisons difficult. Generally, such experiments have relied on traditional approaches to analyze gene expression that often restrict the experimenter to studying only a few mRNA species, whereas a behavior as complex as thirst may be influenced by changes in multiple genes. The present experiments utilized quantitative receptor autoradiography and mRNA expression profiling to identify and compare AngII receptors and their mRNA levels as well as other components of the RAS in female rat pituitary and hypothalamic-thalamic-septal (HTS) tissue samples. This relatively new approach to the study of gene expression permits the simultaneous comparison of multiple genes from a single tissue sample. These studies revealed that ovariectomized (OVX) female rats treated with estradiol benzoate (EB) had a 30%-40% reduction in the levels of AT(1) receptor mRNA in pituitary and HTS samples as compared to OVX, control animals. In the pituitary, the mRNA levels for angiotensinogen (AGT) were increased by 45% following estrogen administration. In addition, a reduction in [125I]-AngII binding to AT(1) receptors in the pituitary and the subfornical organ was measured following estrogen treatment. These results suggest that estrogen may modulate the pituitary and central RAS through a coordinate regulation of the angiotensin receptors and the levels of newly synthesized AngII.

Animals↗

PubMed1999

Ovarian steroid regulation of angiotensin II-induced water intake in the rat.

Spontaneous water intake as well as thirst elicited by ANG II has been shown to be influenced by the stage of the estrous cycle in the female rat. In these experiments, the contribution of each of the ovarian steroid hormones to the regulation of water intake was examined. Ovariectomized female rats were given replacement doses of estrogen, progesterone, or both, and their responsiveness to an intracerebroventricular injection of ANG II was tested. Forty-eight-hour treatment with estradiol benzoate attenuated ANG II-induced thirst by as much as 70% compared with control animals. The effect of estrogen on drinking was dose dependent and could be completely blocked with concurrent administration of the antiestrogen CI-628. In contrast, progesterone, given alone or after estrogen, did not significantly affect ANG II-induced water intake when animals were tested at 4 or 24 h after steroid administration. A central interaction between the peptide hormone ANG II and estrogen, involving a genomic mechanism, may underlie the cyclicity in water intake behavior observed in the rat.

Angiotensin II↗

PubMed1999

Sodium depletion and aldosterone decrease dopamine transporter activity in nucleus accumbens but not striatum.

Motivated behaviors, including sodium (Na) appetite, are correlated with increased dopamine (DA) transmission in the nucleus accumbens (NAc). DA transporter (DAT) modulation affects DA transmission and may play a role in motivated behaviors. In vivo Na depletion, which reliably induces Na appetite, was correlated with robust decreases in DA uptake via the DAT in the rat NAc with rotating disk electrode voltammetry [1,277 +/- 162 vs. 575 +/- 89 pmol. s-1. g-1; Vmax of transport for control vs. Na-depleted tissue]. Plasma aldosterone (Aldo) levels increase after in vivo Na depletion and contribute to Na appetite. Decreased DAT activity in the NAc was observed after in vitro Aldo treatment (428 +/- 28 vs. 300 +/- 25 pmol. s-1. g-1). Neither treatment affected DAT activity in the striatum. These results suggest that a direct action of Aldo is one possible mechanism by which Na depletion induces a reduction in DAT activity in the NAc. Reduced DAT activity may play a role in generating increased NAc DA transmission during Na appetite, which may underlie the motivating properties of Na for the Na-depleted rat.

Aldosterone↗

PubMed1998

Behavioral and endocrine change following chronic predatory stress.

Adult male rats showed very high levels of crouching when exposed to a cat, with suppression of the nondefensive behaviors (e.g., lying, locomotion, rearing) that were shown by toy cat-exposed controls. The crouching of cat-exposed rats declined slightly but reliably with increasing time within daily 60-min exposure sessions. However, the lack of a reliable cat-exposure x days interaction for crouching over the 20 days of testing indicated minimal habituation of the rats' defensive response to the cat over this exposure schedule, although rat and cat were separated by a wire mesh screen, precluding contact and pain. Following the 20th day of exposure, cat-exposed rats showed reliably higher basal plasma corticosterone levels, suggesting a lack of habituation of this stress-linked response as well. Adrenal weights were also higher and thymus weights lower in these animals compared with controls, while spleen and testes weights and testosterone levels were not reliably different. Of the 13 cat-exposed subjects, 6 (and a single control) failed to show a 10 microg/mL corticosterone (CORT) increase in response to an acute restraint stressor. In 3 of these 6 cat-exposed rats, the failure to meet this criterion was attributable to a low level of CORT following restraint, suggesting failure of the normal CORT surge to the acute restraint stressor. These findings of organ weight changes, enhanced basal CORT, and reduced CORT response to stress in a subgroup of animals are similar to many of the phenomena obtained with other intense, chronic stressors such as subordination, and suggest that repeated predator exposure produces a pattern of intense behavioral and endocrine response that is very slow to habituate. Because it is a natural stressor for both male and female subjects, and one for which pain and even handling of the subject is unnecessary, cat exposure may provide a particularly relevant and adaptable paradigm for research involving analysis of gender effects on the stress response.

Animals↗

PubMed1998

Mapping of RNA accessible sites for antisense experiments with oligonucleotide libraries.

Antisense experiments are often complicated by the lack of reliable methods for selecting effective antisense sequences. Chimeric oligodeoxynucleotide (ODN) libraries and ribonuclease H (RNase H) were used to identify regions on the 1253 nucleotide angiotensin type-1 receptor (AT1) mRNA that are accessible to hybridization with antisense ODNs. Phosphorothioate antisense ODNs targeted against accessible sites reduced AT1 receptor levels by at least 50% in cell culture. ODNs to 4 sites produced a 70% to 80% reduction. In contrast, most sequences targeted between accessible sites were ineffective. When injected into the brains of rats, ODNs targeted to accessible sites reduced AT1 (by 65%) but not AT2 receptor levels. Additionally, AT1 receptor function as measured by agonist-induced water intake, was significantly attenuated in these rats. ODNs directed between accessible sites were ineffective at suppressing water intake. RNA mapping can be applied to any RNA target to facilitate selection of multiple, active antisense sequences for cell culture and in vivo experiments.

Animals↗

PubMed1998

Regulation of glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acids by selective agonists in the rat hippocampus.

Adrenal steroids can have prodigious effects on the structure, function, and survival of hippocampal neurons. In the rat hippocampus, the actions of adrenal steroids are mediated by two receptor types, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Using in situ hybridization, we have examined the regulation of the messenger RNAs (mRNAs) encoding the glucocorticoid and mineralocorticoid receptors, by aldosterone, which acts selectively through MR, and by RU28362, which acts selectively through GR. Our results demonstrate that there is autoregulation of each receptor subtype, such that activation of GR regulates GR mRNA levels and MR activation regulates MR mRNA expression. In addition, there is evidence that aldosterone, acting through MR, can affect the expression of GR mRNA. The extent to which a specific agonist can produce a significant change in the expression of a particular steroid receptor mRNA varies between the different subfields of the hippocampus.

Adrenalectomy↗

PubMed1998

Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus.

Adrenal steroids and neurotrophic factors are important modulators of neuronal plasticity, function, and survival in the rat hippocampus. Adrenal steroids act through two receptor subtypes, the glucocorticoid receptor (GR) and the mineralocorticoid receptor, and activation of each receptor subtype has distinct biochemical and physiological consequences. Adrenal steroids may exert their effects on neuronal structure and function through the regulation of expression of neurotrophic and growth-associated factors. We have examined adrenal steroid regulation of the neurotrophins brain-derived neurotrophic factor, neurotrophin-3, and basic fibroblast growth factor, as well as the growth associated protein GAP-43, through activation of GR or mineralocorticoid receptor with selective agonists. Our findings indicated that in CA2 pyramidal cells, adrenalectomy resulted in decreases in the levels of basic fibroblast growth factor and neurotrophin-3 messenger RNA, which were prevented by activation of mineralocorticoid but not glucocorticoid receptors. Adrenalectomy-induced increases in GAP-43 and brain-derived neurotrophic factor messenger RNA levels could be blocked by activation of glucocorticoid receptors in CA1, but not in CA3, pyramidal cells. Thus the extent to which adrenal steroids regulate hippocampal neurotrophic and growth-associated factors, appears to be dependent both on the adrenal steroid receptor subtype activated and on the hippocampal subregion examined.

Adrenalectomy↗

PubMed1997

Chronic social stress alters levels of corticotropin-releasing factor and arginine vasopressin mRNA in rat brain.

In the visible burrow system model of chronic social stress, male rats housed in mixed-sex groups quickly form a dominance hierarchy in which the subordinates appear to be severely stressed. A subgroup of subordinates have an impaired corticosterone response after presentation of a novel restraint stressor, leading to their designation as nonresponsive subordinates. To examine the mechanism underlying the blunted corticosterone response in these animals, in situ hybridization histochemistry was used to quantify corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) mRNA expression in the brain. In two separate visible burrow system experiments, the nonresponsive subordinates expressed a significantly lower average number of CRF mRNA grains per cell in the paraventricular hypothalamic nucleus compared with stress-responsive subordinates, dominants (DOM), or cage-housed control (CON) rats. The number of CRF mRNA labeled cells was also significantly lower in nonresponders than in responsive subordinates or DOM. In the central amygdala, CRF mRNA levels were increased in both groups of subordinates compared with CON rats, whereas responsive subordinates exhibited higher levels than the DOM rats as well. AVP mRNA levels did not vary with behavioral rank in any subdivision of the paraventricular hypothalamic nucleus. In the medial amygdala, the number of cells expressing AVP mRNA was significantly greater in CON rats compared with both groups of subordinates, although the average number of AVP mRNA grains per cell did not vary with rank. In addition, the number of AVP-positive cells significantly correlated with plasma testosterone level.

Amygdala↗

PubMed1997

Brain oxytocin receptor antagonism disinhibits sodium appetite in preweanling rats.

Previous studies have shown that preweanling rats do not express an endogenous sodium appetite until postnatal day 12. The present studies tested the hypothesis that prior to 12 days of age sodium appetite, induced by either central administration of angiotensin II (AngII) or adrenalectomy, is inhibited by endogenous oxytocin (OT). After 9- or 10-day old animals were given a central injection of either an OT receptor antagonist or vehicle, they were infused intraorally with 4% sodium chloride which the animals could either swallow or reject. Intake was measured as the increase from initial body weight. There was very little sodium consumption by vehicle-injected animals that received sham surgery or adrenalectomy; however, the OT receptor antagonist significantly elevated sodium consumption in adrenalectomized animals. The OT antagonist also potentiated sodium intake after AngII pretreatment. These results suggest that the neurochemical circuits necessary for the expression of sodium appetite are present and functional as early as postnatal day 9; however, until 12 days of age this behavior is suppressed by endogenous OT.

Adrenalectomy↗

PubMed1997

Long-term corticosteroid treatment but not chronic stress affects 11beta-hydroxysteroid dehydrogenase type I activity in rat brain and peripheral tissues.

Long-term treatment (21 days) of male rats with corticosterone in the drinking water caused a significant increase in the activity of the NADP-dependent form of 11beta-hydroxysteroid dehydrogenase (11-HSD1) in the pituitary, thymus, and spleen, (marginally in the hippocampus, amygdala and lymph nodes), without having any effect in a number of other central and peripheral tissues. In contrast, repeated restraint stress, although increasing plasma corticosterone to the same level as that observed after its administration, failed to change the activity of this key regulatory enzyme, which allows aldosterone to exert its specific effects in the presence of a large excess of corticosterone. This resistance to elevation in 11-HSD activity was also observed in the thymuses of subordinate rats during social stratification in a visible burrow system. In both cases, the circulating levels of corticosterone were much higher in stressed rats than in control animals. Factors which might account for these differences in response are discussed and compared with the situation in intact cells where, unlike in tissue homogenates, the reduction of 11-dehydrocorticosterone to corticosterone (reductase activity) appears to predominate.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1996

Blockade of central angiotensin II type 1 and type 2 receptors suppresses adrenalectomy-induced NaCl intake in rats.

Removal of the adrenal glands, the main site for the synthesis of aldosterone, produces an intake of sodium that is essential for survival. Using central blockade of angiotensin II (Ang II) receptors with SarIle Ang II, previous studies have shown that this intake depends on the stimulation of the brain angiotensin system. In the present study, using intracerebroventricular injection of specific antagonists of Ang II type 1 (AT1) or type 2 (AT2) receptors (losartan and PD 123319, respectively), we confirm that activation of brain angiotensin is essential for the expression of adrenalectomy-induced NaCl intake. Moreover, we show that (a) AT1 but not AT2 receptor blockade alone suppresses NaCl intake and (b) doses of AT1 and AT2 receptor antagonists that separately have no effect on NaCl intake, suppress the behavior when combined. It is proposed that AT1 receptors mediate the natriorexigenic effect of Ang II and that AT2 receptors have a permissive role on AT1 receptor stimulation.

Adrenalectomy↗

PubMed1996

Immunological analysis of angiotensin AT2 receptors in peripheral tissues of neonatal and adult rats.

The peptide hormone angiotensin II (Ang II) is an important regulator of cardiovascular and body fluid homeostasis. Circulating Ang II mediates its physiological actions by activating Ang II receptors in both the periphery and the brain. Previous studies have demonstrated that Ang II receptor expression is high in neonates and decreases to adult levels as the animal matures. A greater proportion of this decline is due to reduced expression of the Type 2 (AT2) receptor subtype. In order to further investigate the expression of this receptor subtype, AT2-directed antisera were utilized to determine the expression of AT2 receptors in both neonatal and adult rat peripheral tissues by immunoblot analysis. The pattern of AT2 receptor immunoreactivity was largely consistent with previous studies employing autoradiographic and radioligand binding assays in peripheral tissues. However, AT2 receptor immunoreactivity was not seen in the adrenal, despite earlier reports of AT2 receptor expression in this peripheral tissue. These immunohistochemical studies also suggested that AT2 receptors undergo tissue-specific post-translational processing during development. Collectively, these results identify immunoreactive AT2 receptor populations in neonatal and adult rat peripheral tissues and further strengthen the hypothesis of AT2 receptor heterogeneity.

Adrenal Glands↗

PubMed1996

Chronic social stress produces reductions in available splenic type II corticosteroid receptor binding and plasma corticosteroid binding globulin levels.

Adult male and female rats were housed for 2 weeks in a Visible Burrow System resulting in the development of strong dominant-subordinate relationships among the male rats. Neuroendocrine measures indicated that the subordinate rats, and to a lesser extent dominant rats, experienced chronic HPA axis hyperstimulation during the 2 week experience. This paper focuses on the consequences of this chronic social stress on cytosolic type II corticosteroid receptor binding in the spleen. In the first study, rats were adrenalectomized 18 h prior to sacrifice in order to measure total cellular receptor protein levels in each animal. In spite of the severity of the social stress, there was no decrease in splenic type II corticosteroid receptor binding levels in these short-term adrenalectomized animals. In the second study, rats were left adrenal-intact. Corticosteroid receptor levels in these adrenal-intact animals reflect the level of receptors (available receptors) that were unoccupied by endogenous hormone at the time of sacrifice. Both subordinate and dominant rats had fewer available splenic type II receptors than control rats, suggesting that a greater proportion of receptors in subordinate and dominant rats were occupied and activated by endogenous hormone at the time of sacrifice than in control rats. The differences in available receptor levels were not a function of total plasma corticosterone levels at the time of sacrifice (mean corticosterone levels were the same for control and subordinate rats). Instead, the differences in available receptor levels may have been a function of plasma corticosteroid binding globulin (CBG) levels which regulate free corticosterone levels. There was a large reduction in plasma CBG levels of subordinate (-70%) and dominant (-40%) rats relative to control rats, and there was a significant correlation between plasma CBG level and available type II receptors in the spleen. These results suggest that a decrease in CBG levels as a result of chronic social stress led to greater access of free corticosterone hormone to type II receptors in the spleen than is typically present in rats under basal or acute stress conditions. This result illustrates one mechanism by which chronic stress may have a greater impact than acute stress on splenic immune function.

Animals↗