Biomedical subjects

R L Hauger

Publications and source records attributed to R L Hauger.

At least 55 records · Page 3Linked to original sources

PubMed1994

Age-related alterations of hypothalamic-pituitary-adrenal axis function in male Fischer 344 rats.

Aging is frequently associated with changes in physiological and cognitive processes. Among these changes is a distinct dysregulation of the hypothalamic-pituitary-adrenal axis. In the current experiments, aspects of hypothalamic-pituitary-adrenal axis function were compared in young (3- to 4-month-old) and aged (21- to 24-month-old) Fisher 344/N male rats. Basal ACTH and corticosterone levels during the circadian trough were elevated in aged compared to young rats. During the evening peak of the circadian cycle, plasma ACTH levels in the young and aged rats were comparable; however, aged rats had significantly lower corticosterone levels than young rats. Stimulus-induced secretion of pituitary-adrenal hormones was attenuated in aged rats. The ACTH response to hemorrhage in the aged group was only 45 +/- 3% of the hemorrhage response in young rats. Pituitary responsiveness to an iv CRF challenge was 58 +/- 6% of that in the young population. These changes were associated with a 38 +/- 5% loss of anterior pituitary CRF receptor number in the aged population. Changes in the hypothalamic regulation of pituitary-adrenal function were also evident in the aged rats. Hypophysial-portal blood concentrations of CRF were significantly greater in aged (56 +/- 6 pM) compared to young rats (37 +/- 4 pM; P < 0.02, by two-tailed unpaired t test; n = 8/group), whereas portal levels of arginine vasopressin were significantly reduced in aged (0.56 +/- 0.01 nM) compared to young rats (0.89 +/- 0.01 nM; P < 0.01, by two-tailed unpaired t test; mean +/- SEM; n = 8/group). Portal CRF responses to hemorrhage were significantly (P < 0.01) greater in aged rats, whereas hemorrhage-stimulated increases in portal AVP levels were significantly (P < 0.01) reduced in the aged group compared to those in the young rats. Finally, regional assay of CRF content demonstrated significant reductions in the median eminence and frontal cortex of aged rats compared to young rats, whereas in situ hybridization analysis failed to reveal age-related differences in paraventricular CRF mRNA levels. Overall, these observations are consonant with the hypothesis that senescence is associated with hypothalamic CRF hypersecretion and a consequent down-regulation of corticotrope CRF receptor.

Adrenocorticotropic Hormone↗

PubMed1993

Benzodiazepines antagonize central corticotropin releasing hormone-induced suppression of natural killer cell activity.

Benzodiazepines have anxiolytic properties and attenuate behavioral stress responses induced by corticotropin releasing hormone (CRH). To evaluate the effect of benzodiazepines on CRH-induced immune suppression, potent centrally acting benzodiazepines were administered prior to central infusion of CRH (i.c.v.; 1.0 microgram). CRH induced a significant (P < 0.01) reduction of splenic natural killer cell activity which was completely antagonized by pretreatment with either diazepam or alprazolam.

Alprazolam↗

PubMed1993

High intracerebral levels of CRH result in CRH receptor downregulation in the amygdala and neuroimmune desensitization.

Corticotropin-releasing hormone (CRH) acts at the pituitary level to increase ACTH secretion and, within the central nervous system, to stimulate the sympathoadrenomedullary axis and behavioral activity. In addition, the central administration of CRH has been reported to reduce cellular immunity in the periphery. This study investigated the temporal relationship between CRH receptor regulation and the changes in splenic natural killer (NK) cell and pituitary-adrenocortical hormone responses to a single intracisternal (IC) CRH challenge (acute CRH) 24 h after chronic CRH pretreatment (5 nmol/day IC CRH for 4 days). Chronic CRH significantly decreased by 44.2 +/- 7.8% (P < 0.01) the CRH receptor concentration (beta max) in the amygdala. In contrast, the CRH receptor concentration of the anterior pituitary in the chronic CRH group was similar to the pituitary CRH receptor concentration in chronic saline controls. The immunoreactive-CRH concentration of the amygdala measured 24 h after the last IC CRH injection was not different from brain CRH levels in controls receiving chronic saline pretreatment. Consequently, the downregulation of amygdala CRH receptors occurred after transient increases in intracerebral CRH levels and did not result from ex vivo receptor occupancy by residual exogenous CRH sequestrated in brain tissue at the time of the CRH binding assay. Pretreatment with chronic CRH completely abolished the ability of a central CRH injection to suppress splenic NK activity; whereas, pituitary-adrenal responses to a superimposed acute CRH challenge were not significantly altered by chronic CRH pretreatment. These results suggest that the desensitization of the brain processes mediating CRH-induced suppression of splenic NK cytotoxicity is temporally correlated with CRH receptor downregulation in the amygdala but independent of pituitary-adrenal activation. These findings represent the first in vivo demonstration of homologous downregulation of extrahypothalamic CRH receptors and provide further evidence for the role of central CRH in the modulation of immune function.

Amygdala↗

PubMed1993

Corticotropin-releasing factor in the paraventricular nucleus modulates feeding induced by neuropeptide Y.

Central administration of neuropeptide Y (NPY) exerts a potent orexigenic effect in rats, whereas injection of corticotropin-releasing factor (CRF) suppresses food intake. Anatomical evidence of NPY-containing terminals located in close proximity to CRF-containing neurons and terminals of the hypothalamus and amygdala suggests possible interactions of these neuropeptide systems in food-intake regulation. The present study examined the effect of local administration of the CRF antagonist, alpha-helical CRF9-41, or peripheral treatment with dexamethasone on NPY-induced hyperphagia. Injection of a 250-ng dose of alpha-hel CRF within the paraventricular nucleus (PVN) of the hypothalamus significantly potentiated the feeding induced by a 500-ng dose of NPY injected into the same locus. In contrast, feeding induced by administration of the 500-ng dose of NPY into the ventromedial hypothalamus (VMH) was not modified by intra-VMH pre-treatment with a 250-ng dose of CRF antagonist. No effects of NPY or alpha-hel CRF on feeding were observed after administration into the central nucleus of the amygdala. Systemic pre-treatment with the synthetic glucocorticoid dexamethasone at a dose known to downregulate the function of CRF neurons in the PVN (100 micrograms/kg) enhanced feeding induced by intra-PVN administration of a 500-ng dose of NPY. These results suggest that hypothalamic CRF systems in the PVN exert inhibitory control over NPY-induced food intake.

Animals↗

PubMed1993

Pituitary-adrenal axis responses to acute amphetamine in the rat.

After acute administration of amphetamine (AMPH), a characteristic behavioral response occurs in the rat, involving increased locomotion and stereotyped licking, grooming, and biting. AMPH administration also activates several neuroendocrine systems, including the pituitary-adrenal axis. Because recent evidence has supported a role for glucocorticoids in modulating the behavioral response to AMPH, the purpose of the present study was to examine the relationship between behavioral and hypothalamic-pituitary-adrenal (HPA) responses to AMPH and determine the physiological substrates responsible for the AMPH-induced release of adrenal steroids. AMPH administration produced the often-reported "inverted-U" shaped behavioral response. Specifically, locomotion was increased by low doses (0.5-1.0 mg/kg, SC) significantly more so than by the highest dose (5.0 mg/kg, SC), which instead elicited intense focused stereotyped movements. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were increased by AMPH in a monotonic dose-response function, with highest levels measured in rats exhibiting the most intense stereotyped behaviors. Plasma ACTH levels then declined 10-30 min after AMPH administration, while AMPH-induced locomotion and stereotyped behavior persisted well beyond this period. In a parallel study, AMPH failed to elevate plasma levels of vasopressin, an important ACTH secretagogue, and AMPH reduced levels of corticotropin-releasing factor (CRF) immunoreactivity in the median eminence, providing indirect evidence of CRF release from this region. AMPH-stimulated ACTH and corticosterone release were prevented by immunoneutralization of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1993

Sympathetic alterations after sodium restriction and short-term captopril administration.

OBJECTIVES: The purpose of this study was to examine the effects of short-term captopril therapy during sodium restriction on several markers of the sympathetic nervous system, including plasma norepinephrine, neuropeptide Y, beta-adrenergic receptors and cortisol. BACKGROUND: Recent studies suggest that the therapeutic effects of converting enzyme inhibitors involve not only the renin-angiotensin and prostaglandin systems but also the sympathetic system. METHODS: Twelve hypertensive and 20 normotensive men were studied after 2 5-day hospital stays during which they consumed a 10-mEq sodium diet and received captopril (25 mg twice daily) or placebo in a double-blind crossover study. RESULTS: Captopril decreased neuropeptide Y (p < 0.05) and angiotensin II (p < 0.01) and increased isoproterenol-stimulated cyclic adenosine monophosphate (AMP) in lymphocytes (p < 0.03), plasma norepinephrine (p < 0.02), cortisol (p < 0.05) and renin (p < 0.001) in both hypertensive and normotensive subjects. Hypertensive subjects had an increased beta-adrenergic receptor density (p < 0.02) and a greater decrease in diastolic blood pressure compared with normotensive subjects (p < 0.02). CONCLUSIONS: The results of this study suggest that the short-term therapeutic effects of captopril may involve concerted changes in key components of the sympathetic nervous system. These findings, such as decreased neuropeptide Y combined with increased norepinephrine and beta-adrenergic receptors, are compatible with the observation of increased cardiac output and decreased peripheral resistance after short-term angiotensin-converting enzyme inhibition.

Analysis of Variance↗

PubMed1993

Regulation of pituitary corticotropin releasing hormone (CRH) receptors by CRH: interaction with vasopressin.

The physiological regulation of ACTH secretion is largely dependent on the interactive effects of CRH and vasopressin (VP) in the pituitary corticotroph. The importance of the magnocellular and parvicellular hypothalamic systems as a source of VP for pituitary regulation was studied by analyzing the effects of endogenous activation of these systems or VP infusion on the ability of CRH to regulate its receptor sites in the anterior pituitary. CRH receptors were measured by binding of [125I]Tyr-ovine CRH to membrane-rich fractions of anterior and neurointermediate pituitary lobes. Minipump infusion of 100 ng/min CRH for 48 h caused a 40% decrease in the anterior pituitary CRH receptor concentration. Simultaneous infusion of VP markedly potentiated the effect of CRH, but only at doses that elevated plasma VP to levels in the range of those in the pituitary portal circulation. Activation of the magnocellular vasopressinergic system by 60 h of water deprivation increased plasma VP levels from 0.5 +/- 0.1 to 11.8 +/- 0.6 pg/ml, but had no effect on the anterior pituitary CRH receptor concentration in control rats or animals receiving CRH infusion (100 ng/min for 48 h). The CRH receptor concentration was significantly increased in neurointermediate pituitary membranes from water-deprived rats. When the parvicellular vasopressinergic system was activated by 14 days of repeated restraint stress, there was a significant enhancement in the ability of CRH to decrease anterior pituitary CRH receptors (33% and 62% in control and stressed rats, respectively). The concomitant infusion of 200 ng/min of the VP antagonist [(mercapto cyclopentamethylene propionic acid)-[methyl-tyrosine]arginine VP] during the CRH infusion in chronically stressed rats significantly reduced the magnitude of the pituitary CRH receptor loss from a 62% to a 43% decrease (P < 0.01). In conclusion, exogenous VP modulates pituitary CRH receptor regulation by CRH only at doses sufficiently high to provide peripheral VP concentrations in the range of the circulating levels in hypophysial-portal blood. Furthermore, the demonstration that chronic endogenous activation of the parvicellular, but not the magnocellular, vasopressinergic system enhances the down-regulatory effect of CRH on anterior pituitary CRH receptors is in support of a critical role of parvicellular VP in the control of the corticotroph function.

Adrenocorticotropic Hormone↗

PubMed1993

Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers.

Neuroendocrine and platelet markers of serotonin (5-hydroxytryptamine, 5-HT) receptor functioning are useful tools for studying the downregulation of 5-HT receptors, a leading hypothesis for the mechanism of action of antidepressant drugs. The 5-HT releaser fenfluramine raises body temperature as well as plasma concentrations of ACTH, cortisol, and prolactin. Pretreatment with the 5-HT1 antagonist pindolol did not block the hyperthermic response to fenfluramine, mediating its actions via non-5-HT1 receptor subtypes (presumably 5-HT2/1C). We observed blunted hyperthermic responses to fenfluramine in unmedicated patients with major depressive disorder. We also observed that the neuroendocrine responses to fenfluramine were decreased by chronic treatment with the tricyclic antidepressant nortriptyline but not by chronic treatment with tricyclic antidepressant nortriptyline but not by chronic treatment with adinazolam, a triazolobenzodiazepine with purported antidepressant activity. IC50 values for ketanserin inhibition of 5-HT-induced platelet shape change response, a marker of 5-HT2/1c receptors, were elevated after nortriptyline treatment in depressed patients, and this increase could be accounted for by those subjects who responded well to antidepressant treatment. Adinazolam treatment did not alter the platelet shape change response. Our data suggest that downregulation of 5-HT2/1c receptors may be linked to the clinical response of depressed patients treated with nortriptyline.

Anti-Anxiety Agents↗

PubMed1992

Desmethylimipramine attenuates cocaine withdrawal in rats.

Depression and anhedonia are two major symptoms of cocaine withdrawal in humans. Hence, pharmacological treatments effective in depression might also alleviate the symptoms of cocaine withdrawal. In the present study, the effects of acute and repeated administration of a tricyclic antidepressant, desmethylimipramine (DMI), were investigated in naive and cocaine-withdrawing rats. An animal model of cocaine withdrawal was used that employs the elevation in intracranial self-stimulation (ICSS) thresholds following the termination of prolonged periods of cocaine self-administration as a measure of an animal's "anhedonic" state. The influence of chronic DMI treatment on beta-adrenergic receptor binding and affinity was also correlated with the behavioral signs of cocaine withdrawal. Neither acute nor repeated DMI treatment influenced reward functions in rats that were not undergoing cocaine withdrawal. However, repeated DMI treatment significantly down-regulated beta-adrenergic receptors, and shortened the duration of the post-cocaine "anhedonia" (elevation in thresholds). Furthermore, the magnitude of the beta-adrenergic receptor down-regulation correlated significantly with the degree of effectiveness of DMI treatment in reversing the post-cocaine "anhedonia". However, chronic DMI treatment did reduce the amount of cocaine self-administered by the animals. The reversal of the post-cocaine anhedonia in this animal model of cocaine withdrawal by chronic DMI treatment demonstrates the potential usefulness of the model in identifying new pharmacotherapies for cocaine withdrawal. In addition, the results indicate that tricyclic antidepressants may be able to ameliorate some of the symptoms of cocaine withdrawal.

Analysis of Variance↗

PubMed1992

Regulation of the anorectic drug recognition site during glucoprivic feeding.

The acute effects of 2-deoxy-D-glucose (2-DG)-induced glucoprivic feeding on the anorectic drug recognition site and Na+K(+)-ATPase in the brain were examined in adult rats and in lean and genetically obese mice. The marked hyperglycemia and the induction of feeding caused by the administration of 2-DG to satiated rats and lean mice were associated with significant increases in Na+K(+)-ATPase activity, and in [3H]ouabain binding and [3H]mazindol binding to the anorectic drug recognition site in hypothalamic membranes. Basal and 2-DG-stimulated levels of blood glucose were significantly correlated to the levels of hypothalamic [3H]ouabain (r = + .91, p less than 0.01) and [3H]mazindol (r = + .87, p less than 0.01) binding. A significant correlation (r = .74, p less than 0.05) was also observed between [3H]mazindol binding and [3H]ouabain binding supporting the hypothesis that these hypothalamic binding sites are functionally coupled in their response to circulating glucose. Following the intracerebroventricular (ICV) administration of the diabetogenic drug alloxan, 2-DG did not stimulate feeding or increase [3H]mazindol and [3H]ouabain binding sites in the hypothalamic paraventricular area. Since 2-DG still caused hyperglycemia in alloxan-treated rats, alloxan-induced inactivation of glucoreceptor mechanisms led to an uncoupling of the anorectic drug recognition site from a hypothalamic glucostat. In genetically obese mice (ob/ob), 2-DG also could not induce feeding or increase hypothalamic [3H]ouabain or [3H]mazindol binding, despite a significant hyperglycemic response. In contrast, 2-DG did increase feeding and the binding of [3H]ouabain and [3H]mazindol to the hypothalamus of lean littermates.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan↗

PubMed1992

Hypothalamic-pituitary-adrenal axis function in the Zucker obese rat.

The development of many endocrine, metabolic, and behavioral abnormalities characteristic of genetically obese Zucker rats is dependent upon the presence of glucocorticoids, the secretion of which is regulated by a neuroendocrine cascade initiated by hypothalamic release of CRF. Recent reports have inferred alterations in central CRF tone as a putative factor contributing to dysregulation of the pituitary-adrenal axis and of metabolic processes in this phenotype. In the current study the hypothalamic CRF system in Zucker lean (FA/?) and obese (fa/fa) phenotypes was functionally evaluated. Neither the stalk median eminence content of CRF or arginine vasopressin (AVP) nor hypothalamic levels of CRF or AVP mRNA differed in the lean and obese phenotypes. No phenotypic differences were observed in either basal or stimulated CRF release from hypothalamic tissue obtained from lean and obese rats. Furthermore, in intact rats the magnitude of pituitary-adrenal responses to various stressors was also similar between phenotypes. However, secretion of CRF and AVP into the hypophysial-portal circulation of obese rats was, respectively, 73% and 35% lower than that of the lean rats. Adrenalectomy was associated with a 3-fold elevation of hypophysial-portal CRF levels in obese rats compared to intact controls. Corticosterone infusion was more effective in suppressing portal CRF levels in adrenalectomized obese compared to adrenalectomized lean rats. Finally, neither CRF receptor number and affinity nor the magnitude of pituitary-adrenal responses to rat CRF challenge (1 micrograms, iv) differed between Zucker phenotypes. These observations lead us to infer that rats of the obese phenotype exhibit reduced hypothalamic CRF tone due to dysregulation of the HPA axis at a site proximal to the hypophysiotropic CRF system that mediates glucocorticoid feedback regulation.

Adrenalectomy↗

PubMed1991

Neuropeptide Y radio-immunoassay: characterization and application.

1. A sensitive and specific neuropeptide Y (NPY) radio-immunoassay has been developed. This radio-immunoassay does not detect the NPY-related peptides pancreatic polypeptide or peptide YY. NPY extracted from rat plasma using sequential C18 sorbent and affinity chromatography co-eluted with synthetic rat NPY when applied to high pressure liquid chromatography. 2. The procedure of stabilization of platelets followed by high speed centrifugation reduced basal values of NPY by 60%, and this may be consistent with removal of platelets that release NPY. Administration of the cholinesterase inhibitor physostigmine (0.3 mg/kg), intravenously, produced a small but significant increase (39%) from basal concentrations of NPY. 3. NPY concentrations in young (2-3-month-old) Sprague-Dawley and Fisher 944 rats were similar; however, NPY concentrations were significantly increased (55%) in 2-year-old Fisher 944 rats. Similar to plasma concentrations of noradrenaline, NPY levels increase with age.

Aging↗

PubMed1991

Response of three hormones to diazepam challenge in sons of alcoholics and controls.

This study evaluates the hypothesis that the decreased reaction to ethanol reported for sons of alcoholics will also be observed following infusions of a benzodiazepine. The investigation compared 37 men who were family history positive for alcoholism with 37 family history negative controls on postinfusion levels of cortisol, prolactin, and growth hormone following 0.12 and 0.20 mg/kg of diazepam given IV over 7 minutes. The results demonstrated no evidence of a decreased response for the sons of alcoholics on the levels of these three hormones.

Adult↗

PubMed1990

CRF receptor regulation and sensitization of ACTH responses to acute ether stress during chronic intermittent immobilization stress.

The relationship between corticotropin releasing factor (CRF) receptors and pituitary-adrenal responses was determined after chronic intermittent immobilization (2.5 h restraint/day) to examine the hypothesis that CRF receptor regulation is involved in the sensitization of the pituitary-adrenocortical axis to novel stimuli during repeated stress. Following the 11-fold stimulation of ACTH secretion on the first day of restraint stress, a desensitization of the pituitary ACTH response to immobilization was observed over the next 9 days of chronic intermittent stress. In contrast, the magnitude of the restraint-stimulated release of corticosterone on the 2nd and 4th day of stress was similar to the day 1 adrenocortical response. Furthermore, the significant stimulation of corticosterone secretion by restraint stress persisted to the 16th day of immobilization (P less than 0.001), even though significant increases in plasma ACTH were absent. The concentration of anterior pituitary CRF receptors was unchanged after a single period of restraint; however, a down-regulation of anterior pituitary CRF receptors was observed following 4 days (P less than 0.001) and 10 days (P less than 0.005) of repeated immobilization stress. CRF receptors in the olfactory bulb were unchanged following acute or chronic restraint stress, consistent with previous observations that brain CRF receptors are neither changed by adrenalectomy, glucocorticoid administration, nor 18-48 h of continuous restraint stress. The concentration of CRF receptors in the intermediate lobe of the pituitary also was not influenced by immobilization stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1990

Cortisol and growth hormone responses to the 5-HT1A agonist gepirone in depressed patients.

The 5-HT1A agonist properties of gepirone were used to test for effects on serum cortisol levels in humans, 90 min after a 10 mg oral dose. Fourteen patients with major depression were tested in a single-blind, within-subjects, placebo design. Serum cortisol levels were significantly higher 90 min after gepirone compared to placebo (p less than 0.05). Baseline Hamilton depression ratings were correlated with the serum cortisol levels after acute administration of gepirone (r = 0.54, p less than 0.05), but not placebo. Cortisol levels after a 10 mg gepirone challenge were significantly (p less than 0.02) attenuated after 3-6 weeks chronic administration of gepirone. These preliminary findings suggest that relatively low doses of gepirone may stimulate human cortisol secretion in depressed patients, and cortisol levels after gepirone challenge may correlate with depression severity. Furthermore, a desensitization to gepirone's effects on cortisol may occur after chronic gepirone administration.

Administration, Oral↗

PubMed1990

TSH response to TRH and family history of alcoholism.

The thyrotropin (TSH) response to intravenous thyrotropin-releasing hormone (TRH) was evaluated in 10 sons of alcoholic fathers (FHP group) and 10 matched controls (FHN group). No differences were observed between the two groups in basal TSH, peak TSH levels, on the incidence of TSH-blunting to TRH. Though there was a trend for a less intense TSH response over time after the TRH infusion, the difference between the family groups was not significant. These results are not consistent with some previous reports of an increased percentage of blunted TSH response to TRH for children of alcoholics. The clinical and research implications of these findings are discussed.

Adolescent↗

PubMed1990

Lithium toxicity: when is hemodialysis necessary?

A case of severe lithium intoxication is presented in which the function of the lithium pump was monitored, and was found to improve as the signs of lithium toxicity abated. The status of the lithium pump may provide an index of the severity of lithium intoxication. Since the lithium pump regulates the extrusion of lithium from the intracellular to the extracellular space, it is argued that the activity of the lithium pump is an index of the severity of lithium intoxication and crucial to the process of detoxification.

Adult↗

PubMed1990

Sympathetic nervous system mediates central corticotropin-releasing factor induced suppression of natural killer cytotoxicity.

Corticotropin-releasing factor (CRF) acts within the brain to elicit changes in neuroendocrine, autonomic and behavioral activity similar to those observed after stress. A reduction of cellular immune function as measured by splenic natural killer cell activity has also been described following the central administration of CRF. In this study we evaluated the role of the sympathetic nervous system in mediating CRF-induced suppression of natural killer (NK) cytotoxicity. Synthetic rat CRF (1.0 microgram) microinjected into the lateral ventricle increased noradrenergic function and reduced NK activity in the rat spleen. Pretreatment of the animals by chemical sympathectomy (6-hydroxy-dopamine, 100 mg/kg i.p. daily over 10 days) produced a greater than 95% reduction of splenic norepinephrine concentration and abolished completely both the CRF-induced increase in plasma catecholamine levels and the reduction in splenic NK activity. In addition, beta adrenergic receptor blockade (either propranolol, 10 mg/kg i.p., or butoxamine, 25 mg/kg i.p. 30 min before i.c.v. infusion) antagonized the CRF-induced reduction in NK activity. Measurement of circulating levels of adrenocorticotrophic hormone and corticosterone demonstrated that activation of the pituitary adrenal axis by CRF was dissociated from changes in NK activity. These findings suggest that the sympathetic nervous system mediates the suppression of splenic NK cytotoxicity after i.c.v. CRF.

Animals↗