Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The behavioral consequences of the central administration of corticotropin releasing hormone (CRH) in rhesus monkeys was determined using food-maintained behavior. Acute doses of CRH (0.003 ng/kg-10 micrograms/kg, i.c.v.), decreased responding for food in a dose- and time-related manner. With intermediate doses, responding occurred at a high rate until food was delivered, and then abruptly ceased for several minutes. Previous studies have attributed similar effects to the noxious properties of certain drugs. Acute doses had no effect on home cage food consumption, body weight, or responding for food on subsequent days. When CRH was given repeatedly for several days, its behavioral suppressant effects increased. Home cage food intake, body weight, and subsequent responding for food decreased for up to 6 weeks before returning to normal. These results suggest that sustained elevations in central levels of CRH can result in a sensitization to its anorexigenic effects, an effect that has not been reported in other species. Because hyperaroused clinical states such as depression and anorexia nervosa are characterized biochemically by hypercortisolism and elevated CRH in CSF, these anorexigenic effects may corroborate a potential role for CRH in affective disorders.
 ...
PMID:Corticotropin releasing hormone produces profound anorexigenic effects in the rhesus monkey. 204 89

CRH is secreted by the placenta into human maternal and fetal plasma during gestation. In the present study plasma CRH was measured in the plasma of five pregnant baboons and their fetuses to ascertain whether the baboon is a suitable model for study of placental CRH. Studies were performed in chronically catheterized animals that exhibited no behavioral or endocrinological signs of stress; maternal animals moved freely about the cage. Mean maternal plasma CRH was 620 +/- 110 pmol/L (2970 pg/mL) at 146 +/- 11 days gestation, and mean fetal plasma CRH was 133 +/- 29 pmol/L (640 pg/mL) at delivery in four animals. Plasma CRH was undetectable (less than 8.5 pmol/L; less than 41 pg/mL) in nonpregnant animals and in animals 8 h after delivery. Maternal and fetal plasma CRH levels in the chronically catheterized baboon were very similar to human maternal and umbilical cord CRH levels at comparable gestational ages. In addition, the majority of maternal plasma CRH eluted in the same position as synthetic human CRH by gel filtration. CRH stimulation tests were performed in the chronically catheterized maternal baboon to investigate whether pituitary-adrenal function during pregnancy is similar to that observed after chronic CRH infusion; blunted ACTH and cortisol responses to acute injections of CRH are observed after chronic CRH infusion. The administration of 0.5 micrograms/kg ovine CRH (oCRH) failed to result in an ACTH or cortisol rise in four pregnant baboons. Baseline ACTH levels were 5.2 +/- 0.4 pmol/L (23.5 pg/mL), and baseline cortisol levels were 800 +/- 55 nmol/L (29.1 micrograms/dL); neither rose after CRH administration. In contrast, 0.5 micrograms/kg oCRH did result in significant ACTH and cortisol elevations in five nonpregnant baboons [ACTH: baseline, 5.9 +/- 1.4; peak, 16 +/- 4.8 pmol/L (P less than 0.05); cortisol: baseline, 430 +/- 55 nmol/L; peak, 960 +/- 200 nmol/L (P less than 0.05)]. In contrast, the administration of a larger dose of oCRH (5.0 micrograms/kg) led to stimulation of ACTH release in five pregnant baboons (baseline, 6.6 +/- 1.3 pmol/L; peak, 34.1 +/- 6.4; P less than 0.001). After this dose cortisol levels also rose in the pregnant animals (baseline = 1040 +/- 30 nmol/L; peak, 1620 +/- 130); however, this response was blunted compared to that in the nonpregnant animals (P less than 0.05). CRH (5.0 micrograms/kg) significantly stimulated both ACTH and cortisol in the nonpregnant animals.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Response to corticotropin-releasing hormone during pregnancy in the baboon. 215 91

In socially organized mammals the predominating stressors are not physical events but arise from the immediate social environment of the animal. Crowding typically evokes social stress reactions with prominent psychosocial components mimicking emotional state alterations. Depending on the nature, intensity and duration of the initial stimuli, they can either reduce or increase the response of the hypothalamic-pituitary adrenal (HPA) axis. In homologous desensitization only stimulation by desensitizing hormone is attenuated, in heterologous desensitization diminished responsiveness to additional activators occurs. Social stress of crowding (21 rats in a cage for 7) for 3, 7, 14 and 21 days considerably reduced the corticosterone response to intracerebroventricular (icv) administration of carbachol, a cholinergic muscarinic receptor agonist due to a homologous desensitization and down-regulation of central muscarinic receptors by an increased secretion of acetylcholine. Crowding stress significantly reduced the HPA response to icv isoprenaline, a beta-adrenergic agonist and clonidine, an alpha2-adrenergic agonist and only moderately diminished the response to phenylephrine -- an alpha1-adrenergic agonist. The stimulatory effect of dimaprit, a nonselective histamine H2-receptor agonist on HPA axis was considerably impaired in crowded rats while the response to 2-pyridylethylamine, a H1-receptor agonist was moderately affected. Social crowding stress did not substantially alter the CRH-induced ACTH and corticosterone response while it suppressed the vasopressin-induced responses. Indomethacin did not change basal plasma ACTH and corticosterone levels, indicating that prostaglandins are not involved in basal regulation of the HPA activity. Inhibition of prostaglandins synthesis by indomethacin significantly diminished the vasopressin-induced HPA response under both basal and social stress conditions, whereas it did affect the CRH-elicited HPA stimulation under both these circumstances. Social stress inhibits the nitric oxide effect on the CRH-induced ACTH response but it does not alter the AVP-induced responses. These results indicate a specific and distinct influences of social crowding stress on the neurotransmitters- neurohormones- prostaglandins- and nitric oxide-induced HPA responses.
 ...
PMID:Social stress adapts signaling pathways involved in stimulation of the hypothalamic-pituitary-adrenal axis. 1057 67

The influence of social disruption stress (SDR) on the susceptibility to endotoxic shock was investigated. SDR was found to increase the mortality of mice when they were challenged with the bacterial endotoxin lipopolysaccharide (LPS). Histological examination of SDR animals after LPS injection revealed widespread disseminated intravascular coagulation in the brain and lung, extensive meningitis in the brain, severe hemorrhage in the lung, necrosis in the liver, and lymphoid hyperplasia in the spleen, indicating inflammatory organ damage. In situ hybridization histochemical analysis showed that the expression of the glucocorticoid receptor mRNA was down-regulated in the brain and spleen of SDR animals while the ratio of expression of AVP/CRH-the two adrenocorticotropic hormone secretagogue, increased. After LPS injection, the expression of pro-inflammatory cytokines, IL-1beta and TNF-alpha, was found significantly higher in the lung, liver, spleen, and brain of the SDR mice as compared with the LPS-injected home cage control animals. Taken together, these results show that SDR stress increases the susceptibility to endotoxic shock and suggest that the development of glucocorticoid resistance and increased production of pro-inflammatory cytokines are the mechanisms for this behavior-induced susceptibility to endotoxic shock.
 ...
PMID:Social stress increases the susceptibility to endotoxic shock. 1128 52

Corticotropin-releasing hormone plays an important role in the coordination of various responses to stress. Previous research has implicated both corticotropin-releasing hormone and the serotonergic system as causative factors in the development and course of stress-related psychiatric disorders such as major depression. To delineate the role of the corticotropin-releasing hormone receptor type 1 (CRH-R1) in the interactions between corticotropin-releasing hormone and serotonergic neurotransmission, in vivo microdialysis was performed in CRH-R1-deficient mice under basal (home cage) and stress (forced swimming) conditions. Hippocampal dialysates were used to measure extracellular levels of serotonin and its metabolite 5-hydroxyindoleacetic acid, and free corticosterone levels to monitor the status of the hypothalamic-pituitary-adrenocortical axis. Moreover, behavioural activity was assessed by visual observation and a scoring paradigm. Both wild-type and heterozygous mutant mice showed a clear diurnal rhythm in free corticosterone. Free corticosterone concentrations were, however, lower in heterozygous mutant mice than in wild-type animals and undetectable in homozygous CRH-R1-deficient mice. Homozygous CRH-R1-deficient mice showed enhanced hippocampal levels of 5-hydroxyindoleacetic acid but not of serotonin during the light and the dark phase of the diurnal cycle, which may point to an enhanced synthesis of serotonin in the raphe-hippocampal system. Moreover, the mutation resulted in higher behavioural activity in the home cage during the light but not during the dark period. Forced swimming caused a rise in hippocampal serotonin followed by a further increase after the end of the stress paradigm in all genotypes. Homozygous and heterozygous mutant mice showed, however, a significantly amplified serotonin response to the forced swimming as compared to wild-type control animals. We conclude that CRH-R1-deficiency results in reduced hypothalamic-pituitary-adrenocortical axis activity, in enhanced synthesis of serotonin during basal conditions, and in an augmented response in extracellular levels of serotonin to stress. These data provide further evidence for the intricate relationship between corticotropin-releasing hormone and serotonin and the important role of the CRH-R1 herein.
 ...
PMID:Corticotropin-releasing hormone receptor type 1-deficiency enhances hippocampal serotonergic neurotransmission: an in vivo microdialysis study in mutant mice. 1180 62

To determine whether docosahexaenoic acid (DHA) affects stress responses in rats, we investigated its influence on several behavioral tests. Female rats were fed a diet deficient in (n-3) fatty acid from mating through pregnancy and lactation. Male pups fed the same diet as their dams were used for experiments. The effects of dietary (n-3) fatty acid deficiency and supplementation with DHA on psychological stress and conditioned-fear stress were investigated. The effect of DHA on psychological stress was examined by an elevated plus-maze test. The (n-3) deficient rats spent significantly (P<0.05) less time in the open arms; after 1 week of supplementation with DHA, they showed a significant (P<0.01) improvement. We then examined the paired effects of DHA and CRH on stress manifestations by an intracerebroventricular (i.c.v.) cannulation and behavior testing. An i.c.v. infusion of CRH (500 pmol) under resting conditions was shown to have stress-inducing effects on behavior such as decreases of rearing, smelling and feeding, and increases of face washing; the supplementation of DHA significantly improved these distress behaviors. Finally, conditioned fear was induced by 40 min forced exposure to a cage in which the rat had experienced footshocks (30 x 1 mA x 1 s) 1 day before. Freezing behavior was dramatically suppressed by the supplementation of DHA, even 48 h after the conditioning treatment. Furthermore, the effect of DHA on the conditioned fear stress response is maintained over a long-term period. The i.c.v. pre-treatment of rats with bicuculline, a GABA(A) receptor antagonist, enhanced the conditioned-fear-induced freezing time in a dose-dependent fashion in the (n-3) fatty acid deficient animals. Significantly, the DHA supplemented group was not affected by the pre-treatment with bicuculline. From these findings, it is concluded that the involvement of DHA in stress responses may act via a GABA(A) receptor-mediated mechanism.
 ...
PMID:Possible regulatory mechanism of DHA-induced anti-stress reaction in rats. 1257 22

The aim of the present study was to determine the effect of social stress and significance of prostaglandins (PG) generated by constitutive and inducible cyclooxygenase (COX-1 and COX-2) in the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by corticotropin releasing hormone (CRH) under basal and social crowding stress conditions. The stressed rats were crowded in groups of 24 to a cage for 3 or 7 days, whereas the control animals were haused in groups of 7 to a cage of the same size. The activity of HPA axis was determined by measuring plasma ACTH and serum corticosterone levels 1 h after i.p. CRH administration. Inhibitors of COX-1, piroxicam (0.2, 2.0, and 5.0 mg/kg), and COX-2, compound NS-398 (0.2 and 2.0 mg/kg), were administered i.p. 15 min prior to CRH (0.1 microg/kg i.p.) to control or crowded rats. The obtained results indicate that social stress for 3 and 7 days markedly intensifies the stimulatory action of CRH on ACTH secretion. Neither piroxicam nor NS-398 induce any significant effect on the CRH-elicited ACTH and corticosterone secretion in non-stressed or crowded rats. Therefore, PG generated by COX-1 or COX-2 do not participate to a significant extent in the stimulation of HPA axis by CRH under either basal conditions or during crowding stress. These results also indicate that the stimulatory action of CRH on ACTH secretion is not only completely resistant to desensitization but is sensitized during social crowding stress. The results contrast with a significant involvement of PG in the vasopressin-induced stimulation of HPA response during crowding stress.
 ...
PMID:Effect of cyclooxygenase inhibitors on the CRH-induced pituitary-adrenocortical activity during crowding stress. 1267 22

The aim of the present study was to compare the effect of social stress on the corticotropin releasing hormone (CRH) and arginine vasopressin (AVP)-induced pituitary-adrenocortical activity. Also the significance of prostaglandins (PG) generated by constitutive and inducible cyclooxygenase (COX-1 and COX-2) in the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by AVP under basal and crowding stress conditions was investigated. The control rats were housed 7 in a standard cage and stressed rats were crowded 24 in a cage of the same size during 7 days. The activity of HPA axis was determined by measuring plasma ACTH and serum corticosterone levels 1 h after i.p. AVP administration. Indomethacin (2.0 mg/kg i.p.), a non-selective COX inhibitor, piroxicam (0.2, 2.0, and 5.0 mg/kg), a more potent COX-1 than COX-2 inhibitor, and compound NS-398 (0.2 and 2.0 mg/kg) a selective COX-2 inhibitor, were administered i.p. 15 min prior to AVP (5.0 microg/kg i.p.) to control or crowded rats. The obtained results indicate that social stress for 7 days considerably inhibits the stimulatory action of AVP on ACTH secretion, while it intensifies the CRH-induced ACTH secretion. Indomethacin, piroxicam and NS-398 significantly diminished the AVP-elicited ACTH and corticosterone secretion in non-stressed rats. None of these COX antagonist induced any significant inhibition of the AVP-induced ACTH and corticosterone secretion in stressed rats. Therefore, PG generated by COX-1 or COX-2 do not participate to a significant extent in the HPA stimulation by AVP during crowding stress. These results suggest that social crowding stress desensitizes the PG stimulatory mechanism which considerably mediates the AVP-induced HPA stimulation under basal conditions. The results contrast with a lack of any involvement of PG in the CRH-induced stimulation of HPA response under basal or crowding stress conditions.
 ...
PMID:Effect of cyclooxygenase inhibitors on the vasopressin induced ACTH and corticosterone response during crowding stress. 1283 25

Antagonists of the corticotropin-releasing hormone receptor type 1 (CRH-R1) are regarded as promising tools for the treatment of stress-related psychiatric disorders. Owing to the intricate relationship between CRH and serotonin (5-HT), we studied the effects of chronic oral treatment of C57Bl6/N mice with the CRH-R1 antagonist NBI 30775 (formerly known as R121919) on hippocampal serotonergic neurotransmission during basal (on 15th day of treatment) and stress (forced swimming; on 16th day of treatment) conditions by in vivo microdialysis. Given the important role of CRH in the regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity and behavior, the effects of NBI 30775 on dialysate-free corticosterone levels, and on home cage and forced swimming-related behavior were also assessed. Chronic administration of NBI 30775 (18.4+/-0.9 mg/kg/day) did not result in alterations in food consumption and body weight. NBI 30775 caused complex changes in hippocampal serotonergic neurotransmission. Whereas no effects on the diurnal rhythms of 5-HT and its metabolite 5-hydroxyindoleacetic acid were found, the responses of the neurotransmitter and its metabolite to 10 min of forced swim stress were reduced and prolonged, respectively. NBI 30775 did not change free corticosterone levels over the diurnal rhythm. Moreover, NBI 30775-treated mice showed a similar forced swim stress-induced increase in corticosterone as observed in the control group. No effects of NBI 30775 on home cage, and swim stress-related active behaviors (climbing, swimming) and immobility were found. Thus, whereas chronic antagonism of CRH-R1 did not compromise HPA axis performance and behavior, distinct changes in serotonergic neurotransmission developed. Owing to the important role of 5-HT in the pathophysiology of mood and anxiety disorders, the latter observation may contribute to the therapeutical efficacy of CRH-R1 antagonists in these illnesses.
 ...
PMID:Altered serotonergic neurotransmission but normal hypothalamic-pituitary-adrenocortical axis activity in mice chronically treated with the corticotropin-releasing hormone receptor type 1 antagonist NBI 30775. 1291 60

An eloquent example of experience-induced neuroplasticity involves the enduring effects of daily "handling" of rat pups on the expression of genes regulating hormonal and behavioral responses to stress. Handling-evoked augmentation of maternal care of pups induces long-lasting reduction of hypothalamic corticotropin releasing hormone (CRH) expression and upregulates hippocampal glucocorticoid receptor levels. These changes promote a lifelong attenuation of hormonal stress responses. We have found previously that handling-evoked downregulation of CRH expression occurs already by postnatal day 9, implicating it as an early step in this experience-induced neuroplasticity. Here, we investigated the neuronal pathways and cellular mechanisms involved. CRH mRNA expression in hypothalamic paraventricular nucleus (PVN) diminished after daily handling but not after handling once only, indicating that "recurrent" handling was required for this effect. Return of handled pups to their cage provoked a burst of nurturing behavior in dams that, in turn, induced transient, coordinate Fos expression in selected regions of the pups' brains. These included central nucleus of the amygdala (ACe) and bed nucleus of the stria terminals (BnST), regions that are afferent to PVN and influence CRH expression there. Whereas handling once sufficed to evoke Fos expression within ACe and BnST, expression in thalamic paraventricular nucleus, a region involved in storing and processing stress-related experience, required recurrent handling. Fos induction in all three regions elicited reduced transcription factor phosphorylation, followed by attenuated activation of CRH gene transcription within the PVN. These studies provide a neurobiological foundation for the profound neuroplasticity of stress-related genes evoked by early-life experience.
 ...
PMID:Neuroplasticity of the hypothalamic-pituitary-adrenal axis early in life requires recurrent recruitment of stress-regulating brain regions. 1672 15


1 2 Next >>