Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the neuroendocrine alterations linked to inborn emotionality in two Wistar rat lines selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, we administered the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. DEX (12:00 M. (noon); 30 microg/kg) resulted in a significantly less efficient suppression of the diurnal increase in the circulating corticotropin (ACTH) levels in the male HAB rats than in the male LAB rats. In addition, plasma ACTH and corticosterone responses to subsequent CRH (7:30 P.M.; 50 ng/kg) were significantly higher in male HAB rats. The rise in ACTH after CRH in the DEX-pretreated male HAB rats points toward an enhanced activity and involvement of endogenous vasopressin synthesized in the hypothalamic paraventricular nucleus (PVN) and acting at pituitary corticotrope cells. We tested this hypothesis by in situ hybridization and in vivo microdialysis, and found an increase in both basal synthesis and release of vasopressin within the PVN of the male HAB rats. As expected, pretreatment with a selective vasopressin type 1 receptor antagonist abolished the CRH-stimulated increase in ACTH secretion in the DEX-pretreated male HAB rats. The results indicate that vasopressin-mediated effects are critically involved in the profound disturbance of the hypothalamic-pituitary-adrenocortical system in male HAB rats, thus revealing striking parallels to the neuroendocrine situation in human depression.
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PMID:Vasopressin mediates the response of the combined dexamethasone/CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders. 1175 Oct 36

In addition to their robust difference in trait anxiety, as illustrated by a variety of behavioral tests, HAB and LAB rats differ in their stress coping strategies, the former being more susceptible and vulnerable to stressor exposure and preferring more passive strategies. HAB rats of either gender show signs of a hyper-reactive hypothalamic-pituitary-adrenocortical (HPA) axis, thus resembling psychiatric patients. As shown by in situ hybridization and microdialysis in freely behaving animals, both the expression and release of vasopressin in the hypothalamic paraventricular nucleus are higher in HAB than in LAB rats, thus contributing to the HPA axis hyperdrive. Accordingly, in HAB animals, administration of a V1 receptor antagonist normalized the pathological outcome of the dexamethasone/corticotropin-releasing hormone test and triggered behavioral changes toward reduced anxiety and active stress coping. Pharmacological validation has revealed signs of depressive-like behavior, as HAB but not LAB rats have shown more active stress coping behavior and a normalized HPA axis after treatment with paroxetine. Of interest, this antidepressant reduced the hypothalamic overexpression of vasopressin; this novel mechanism of action is likely to contribute to paroxetine effects on both behavioral and neuroendocrine parameters. Cross-mating and cross-fostering paradigms showed that the divergent emotionality in HAB vs. LAB rats is determined genetically, rather than postnatally through maternal behavior. As the behavioral and neuroendocrine phenotyping pointed to the vasopressin gene as a candidate gene critically involved in anxiety, preliminary genetic approaches have been focused on this gene, revealing single nucleotide polymorphisms (SNPs) in the promotor area of the vasopressin gene in HAB, but not LAB rats. HAB/LAB rats are thus proving to be a unique animal model to identify and characterize neurobiological, neuroendocrine, and genetic correlates of trait anxiety, and perhaps depression, in humans.
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PMID:High vs low anxiety-related behavior rats: an animal model of extremes in trait anxiety. 1240 13

This review summarises behavioural, neuroendocrine, and genetic characteristics of Wistar rats bred for either high (HAB) or low (LAB) anxiety-related behaviour. Compared to LABs, HAB animals show signs of extreme trait anxiety in a variety of behavioural tests; they further prefer passive coping strategies, indicative of a genetically linked depression-like behaviour, and show signs of increased stress vulnerability. All behavioural parameters associated with trait anxiety are robust and consistent. Resembling psychiatric patients, HAB rats respond to exposure to ethologically relevant stressors with a hyper-reactivity of the hypothalamic-pituitary-adrenal axis and show a pathological outcome of the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) challenge test. Experimental evidence indicates that over-expression and -release of vasopressin in the hypothalamic paraventricular nucleus is responsible for these behavioural and neuroendocrine phenomena, making the neuropeptide gene a candidate gene of trait anxiety/depression. Indeed, preliminary molecular genetic approaches succeeded in identifying polymorphisms in the promoter structure of the vasopressin gene. This may have implications for understanding the molecular basis for individual variations in trait anxiety and for psychopathology.
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PMID:Born to be anxious: neuroendocrine and genetic correlates of trait anxiety in HAB rats. 1277 30

To model aspects of trait anxiety/depression, Wistar rats were bred for extremes in either hyper (HAB)- or hypo(LAB)-anxiety as measured on the elevated plus-maze and in a variety of additional behavioral tests. Similar to psychiatric patients, HAB rats prefer passive stress-coping strategies, indicative of depression-like behavior, show hyper-reactivity of the hypothalamo-pituitary-adrenal axis, and a pathological response to the dexamethasone/corticotropin-releasing hormone (CRH) challenge test. Here we tested central mRNA expression, release patterns, and receptor binding of neuropeptides critically involved in the regulation of both anxiety-related behavior and the HPA axis. Thus, CRH, arginine-8-vasopressin (AVP), and oxytocin (OXT) were studied in brains of HAB and LAB males both under basal conditions and after exposure to a mild emotional stressor. In HAB rats, CRH mRNA was decreased in the bed nucleus of the stria terminalis only. While no significant difference in CRH1-receptor binding was found in any brain area, CRH2-receptor binding was elevated in the hypothalamic paraventricular nucleus (PVN), the ventromedial hypothalamus, and the central amygdala of HABs compared to LABs. AVP, but not OXT, mRNA expression as well as release of the neuropeptide, were higher in the PVN of HABs, whereas AVP V1a-receptor binding failed to show significant differences in any brain region studied. Remarkably, intra-PVN treatment of HABs with the AVP V1-receptor antagonist d (CH(2))(5) Tyr (Me) AVP resulted in a decrease in anxiety/depression-related behavior. The elevated expression and release of AVP within the PVN of HAB rats together with the behavioral effects of the AVP V1-receptor antagonist suggest a critical involvement of this neuropeptide in neuroendocrine and behavioral phenomena associated with trait anxiety/depression.
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PMID:Alterations in central neuropeptide expression, release, and receptor binding in rats bred for high anxiety: critical role of vasopressin. 1294 43

We studied the mechanisms of genetic-early environmental interactions to modulate adult stress-coping and tested the hypothesis that prenatal stress (PS) can differentially alter the consequences of a genetic predisposition to either hyper- or hypo-anxiety. Exposure of male Wistar rats, bred for high (HAB) or low (LAB) anxiety-related behaviour, to PS between pregnancy days 4 and 18 resulted in opposite effects on anxiety in adulthood, i.e. HAB rats became less and LAB rats became more anxious compared with their unstressed controls (plus-maze and holeboard). The high anxiety of HAB controls was accompanied by elevated expression of vasopressin and corticotropin-releasing hormone (CRH) mRNA within the hypothalamic paraventricular nucleus compared with LAB rats. PS reduced CRH mRNA expression in HAB rats but increased vasopressin mRNA expression in LAB rats, which may explain the opposite effects of PS on adult emotionality. Differential effects of PS were also found with respect to hypothalamo-pituitary-adrenal axis reactivity; the hypothalamo-pituitary-adrenal hyper-response in virgin female HAB controls became attenuated after PS, without affecting plasma corticosterone concentrations in LAB rats. Differences in maternal plasma corticosterone measured between pregnancy days 6 and 14 of HAB and LAB dams or differential effects of PS on maternal behaviour can be excluded. In conclusion, exposure of rats with genetically determined high or low emotionality to PS mitigates the extremes in behavioural and neuroendocrine stress-coping, thus allowing adequate and similar behavioural responses to potentially dangerous stimuli in adulthood. Differential effects of PS on the activity of the brain vasopressin and CRH systems might represent possible underlying molecular mechanisms.
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PMID:Prenatal stress: opposite effects on anxiety and hypothalamic expression of vasopressin and corticotropin-releasing hormone in rats selectively bred for high and low anxiety. 1642 Apr 61

Genetic background may influence an individual's susceptibility to, and subsequent coping strategy for, an acute stressor. When exposed to social defeat (SD), rats bred for high (HAB) or low (LAB) trait anxiety, which also differ in depression-like behavior, showed highly divergent passive and active coping behaviors, respectively. HABs spent more time freezing and emitted more ultrasound vocalization calls during SD than LABs, which spent more time rearing and grooming. Although the behavioral data confirmed the prediction that heightened trait anxiety would make rats more prone to experience stress, adrenocorticotropin and corticosterone were secreted to a higher extent in LABs than in HABs. In the latter, Fos expression upon SD was enhanced in the amygdala and hypothalamic areas compared with LABs, whereas it was diminished in prefrontal and brainstem areas.
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PMID:Genetic predisposition to anxiety-related behavior determines coping style, neuroendocrine responses, and neuronal activation during social defeat. 1649 17

Aggression constitutes a central problem in several psychopathologies, including anxiety and depression disorders and antisocial behaviors. In particular, the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis has been associated with aggression-related disorders. The present study assessed whether genetically determined levels of anxiety-related behavior influence the level of intermale aggression and whether this is associated with differences in neuroendocrine responsiveness and neuronal activation in the brain. Adult male Wistar rats bred for high (HAB) or low (LAB) anxiety-related behavior were used, as well as non-selected rats (NAB) with an intermediate anxiety level. LAB residents displayed more aggressive behavior than HAB and NAB residents during the resident-intruder (RI) test. Moreover, an inverse correlation was found between the level of anxiety and the level of aggression. The plasma corticotropin (ACTH) response to RI-test exposure was significantly higher in LABs than in HABs and NABs, indicating that a higher level of aggression was linked to an elevated hormonal stress response. Furthermore, LAB residents showed more neuronal activation in the parvocellular part of the hypothalamic paraventricular nucleus (PVN) than HAB residents 1 h after the RI-test. In addition, a tendency toward a higher number of c-Fos-positive cells in LABs compared with HABs was observed in the medial amygdala, hypothalamic attack area and central amygdala, areas relevant for the regulation of aggression. These data demonstrate that low trait anxiety is correlated with high intermale aggression. Furthermore, the increased neuronal activation of the PVN along with the higher ACTH responsiveness might underlie the display of high aggression.
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PMID:Low inborn anxiety correlates with high intermale aggression: link to ACTH response and neuronal activation of the hypothalamic paraventricular nucleus. 1693 87

The continuum of physiological anxiety up to psychopathology is not merely dependent on genes, but is orchestrated by the interplay of genetic predisposition, gene x environment and epigenetic interactions. Accordingly, inborn anxiety is considered a polygenic, multifactorial trait, likely to be shaped by environmentally driven plasticity at the genomic level. We here took advantage of the extreme genetic predisposition of the selectively bred high (HAB) and low anxiety (LAB) mouse model exhibiting high vs low anxiety-related behavior and tested whether and how beneficial (enriched environment) vs detrimental (chronic mild stress) environmental manipulations are capable of rescuing phenotypes from both ends of the anxiety continuum. We provide evidence that (i) even inborn and seemingly rigid behavioral and neuroendocrine phenotypes can bidirectionally be rescued by appropriate environmental stimuli, (ii) corticotropin-releasing hormone receptor 1 (Crhr1), critically involved in trait anxiety, shows bidirectional alterations in its expression in the basolateral amygdala (BLA) upon environmental stimulation, (iii) these alterations are linked to an increased methylation status of its promoter and, finally, (iv) binding of the transcription factor Yin Yang 1 (YY1) to the Crhr1 promoter contributes to its gene expression in a methylation-sensitive manner. Thus, Crhr1 in the BLA is critically involved as plasticity gene in the bidirectional epigenetic rescue of extremes in trait anxiety.
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PMID:Bidirectional rescue of extreme genetic predispositions to anxiety: impact of CRH receptor 1 as epigenetic plasticity gene in the amygdala. 2451 97

Depression and anxiety disorders are often characterized by altered hypothalamic-pituitary-adrenal (HPA) axis re-/activity. However, the presence of a molecular link between dysbalanced neuroendocrine regulation and psychopathologies is not yet fully established. Earlier, we reported that high (HAB), normal (NAB) and low (LAB) anxiety-related behavior mice express divergent anxiety-related and passive/active coping phenotypes. Here, we studied mechanisms that might contribute to the different HPA axis reactivity observed in HAB, NAB and LAB mice and their involvement in the regulation of anxiety-related behavior and passive/active coping style. We found that HAB mice respond with significantly reduced corticosterone (CORT) secretion to an acute stressful stimulus and a blunted response in the Dex/CRH test compared to NAB and LAB mice. At the molecular level, higher expression of the glucocorticoid receptor (GR/Nr3c1) and decreased corticotropin-releasing hormone receptor 1 (CRHR1) expression were observed in the pituitary of HAB mice. We further analyzed whether these stress mediators differed between the HAB, NAB and LAB lines in limbic system-associated brain regions and whether their interplay contributes to the phenotype. Interestingly, not only in the pituitary but also in almost all brain regions investigated, GR expression was significantly higher in HAB mice. In contrast, the amount of CORT in the brain structures analyzed was significantly lower in these animals. The expression of CRHR1 varied in the prefrontal cortex only. Since glucocorticoids regulate both GR and CRHR1, we treated HAB and NAB mice chronically with CORT. After 6 weeks of administration, reduced anxiety- and depression-like behaviors were observed in HAB mice, whereas increased anxiety was found in NABs. In both groups, GR, but not CRHR1, were significantly reduced. Taken together, our study proposes HAB mice as an animal model of simultaneous features of increased anxiety-related and depression-like behaviors with blunted HPA axis reactivity suggesting a dysregulated GR/CORT system as one key mechanism behind their phenotype.
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PMID:Blunted HPA axis reactivity reveals glucocorticoid system dysbalance in a mouse model of high anxiety-related behavior. 2499 83

This study focused on genetically determined versus acquired factors in shaping anxiety-related behavior by combining cross-breeding and cross-fostering approaches. Via cross-breeding of HAB (high anxiety-related behavior) female and LAB (low anxiety-related behavior) male mice, we obtained F1 hybrids with intermediate anxiety levels carrying genetic characteristics of both parental lines. Pups were raised either by their biological HAB (noncross-fostered control) or foster LAB (cross-fostered) mothers. Compared to controls, 6-week-old offspring raised by LAB mothers showed lower levels of anxiety in the elevated plus-maze and open field, but not the light-dark box, tests. No differences were found in the forced swim test reflecting active versus passive coping. The behavioral changes were associated with increased stress-induced concentrations of plasma corticosterone in cross-fostered animals. The expression of the corticotropin-releasing hormone receptor type I and glucocorticoid receptor genes did not differ in limbic and hypothalamic brain areas between cross-fostered and control mice. The data suggest that LAB-typical maternal care may partially shift behavioral and neuroendocrine characteristics of F1 crosses carrying both HAB and LAB alleles from intermediate toward reduced anxiety-related behavior. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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PMID:Inborn vs. acquired anxiety in cross-breeding and cross-fostering HAB/LAB mice bred for extremes in anxiety-related behavior. 3068 86


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