UNIPROT:P01189 - FACTA Search

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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cocaine administration increases activity at dopamine receptors, increases preprodynorphin (ppDyn) gene expression in the caudate-putamen (CPu), and activates the stress responsive hypothalamic-pituitary-adrenal (HPA) axis. To examine the hypothesis that mu-opioid receptors (MOR) may play roles in these cocaine effects, we tested the effects of acute "binge" pattern cocaine administration in mice with targeted disruption of the MOR gene. Wild-type (+/+) and homozygous MOR-deficient (-/-) mice received three injections of 15 mg/kg cocaine at 1-h intervals. Mice were sacrificed 30 min after the last injection and mRNAs for ppDyn and preproenkephalin (ppEnk) in the CPu and nucleus accumbens (NAc), and for type I corticotropin-releasing hormone receptor (CRH(1) receptor) and pro-opiomelanocortin (POMC) in the hypothalamus and pituitary, were measured by solution hybridization RNase protection assays. Cocaine elevated ppDyn mRNA in the CPu, but not NAc, of both the MOR -/- and wild-type mice. ppEnk mRNA in the CPu, but not NAc, was lower in MOR -/- mice than in wild-type mice following cocaine administration. Hypothalamic CRH(1) receptor and POMC mRNAs were expressed at similar levels in untreated and in cocaine-treated mice of each genotype. However, there were lower basal levels of CRH(1) receptor mRNA in the anterior pituitary of the MOR -/- mice than in wild-type mice and the MOR -/- mice failed to show the cocaine-induced decreases in CRH(1) receptor mRNA found in the wild-type mice. Cocaine activated the HPA axis similarly in MOR -/- and wild-type mice, as reflected in similar increases in plasma corticosterone levels in both genotypes. These results support a specific role for MORs in acute cocaine effects on striatal ppEnk gene expression and fail to support critical roles for these receptors in acute cocaine's effects on either ppDyn gene expression or HPA activation. MOR -/- mice are useful models for studying cocaine effects on ppEnk gene expression that could aid interpretation of the similar postmortem phenomena found in human cocaine addicts.
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PMID:Effects of acute "binge" cocaine on preprodynorphin, preproenkephalin, proopiomelanocortin, and corticotropin-releasing hormone receptor mRNA levels in the striatum and hypothalamic-pituitary-adrenal axis of mu-opioid receptor knockout mice. 1212 43

Cocaine is a highly addictive substance abused worldwide. Its mechanism of action involves initially inhibition of neuronal monoamine transporters in precise brain structures and primarily the dopamine reuptake system located on mesolimbic neurons. Cocaine rapidly increases the dopaminergic neurotransmission and triggers adaptive changes in numerous neuronal circuits underlying reinforcement, reward, sensitization and the high addictive potential of cocaine. Current therapeutic strategies focus on counteracting the cocaine effects directly on the dopamine transporter, through post-synaptic D(1), D(2) or D(3) receptors or through the glutamatergic, serotoninergic, opioid or corticotropin-releasing hormone systems. However, cocaine administration also results in the activation of numerous particular targets. Among them, the sigma(1) (sigma(1)) receptor is involved in several acute or chronic effects of cocaine. The present review will first bring concise overviews of the present strategies followed to alleviate cocaine addiction and animal models developed to analyze the pharmacology of cocaine addiction. Evidence involving activation of the sigma(1) receptor in the different aspects of cocaine abuse, will then be detailed, following acute, repeated, or overdose administration. The therapeutic potentials and neuropharmacological perspectives opened by the use of selective sigma(1) receptor antagonists in cocaine addiction will finally be discussed.
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PMID:Sigma(1) (sigma(1)) receptor antagonists represent a new strategy against cocaine addiction and toxicity. 1220 95

Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalamic neuroendocrine neurones. Adult male rats received a systemic injection of the neuronal tracer Fluorogold (FG) 2 days before fixation, and subsequent double- and triple-labelling immunoflourescence analysis demonstrated that neuroendocrine CART-containing neurones were present in the anteroventral periventricular, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro-opiomelanocortin in the ventrolateral part, but completely absent from neuroendocrine neurones of the dorsomedial part. To assess the possible role of CART as a hypothalamic-releasing factor, immunoreactive CART was measured in blood samples from the long portal vessels connecting the median eminence with the anterior pituitary gland. Adult male rats were anaesthetized and the infundibular stalk exposed via a transpharyngeal approach. The long portal vessels were transected and blood collected in 30-min periods (one prestimulatory and three poststimulatory periods). Compared to systemic venous plasma samples, baseline concentrations of immunoreactive CART were elevated in portal plasma. Exposure to sodium nitroprusside hypotension triggered a two-fold elevation of portal CART42-89 immunoreactivity throughout the 90-min stimulation period. In contrast, the concentration of portal plasma CART immunoreactivity dropped in the vehicle infused rats. The current study provides further evidence that CART is a neuroendocrine-releasing factor with a possible impact on anterior pituitary function during states of haemodynamic stress.
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PMID:Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit. 1258 9

Cocaine- and amphetamine-regulated transcript (CART) has an important action on hypophysiotropic thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) neurons to regulate the hypothalamic-pituitary-thyroid and adrenal axis, respectively. To elucidate the mechanisms by which CART mediates its effect on TRH and CRH neurons, we determined whether the exogenous administration of CART into the cerebrospinal fluid (CSF) phosphorylates the transcription factor, cyclic adenosine 5'-monophosphate response element binding protein (CREB), in the nucleus of TRH and CRH neurons. CART dramatically increased the percentage of phosphoCREB (PCREB) immunolabeled cell nuclei in the hypothalamic paraventricular nucleus (PVN) in fasted as well as fed rats at 10-min postinjection, particularly in the medial parvocellular subdivision of the PVN. Double immunolabelling with CRH antiserum revealed that CART increased the number of CRH neurons containing PCREB from 10.5+/-1.2 % to 87+/-1.2% (P<0.001) in fasting animals and from 3.7+/-0.8% to 74+/-5.3% (P<0.001) in fed animals. In contrast, no significant change was observed in the percentage of proTRH neurons colocalizing with PCREB either in the fasted (11.7+/-1.85%) or fed animals (4.2+/-2.2%) as compared to their respective vehicle controls (2.5+/-1.4% and 4.6+/-1%). Ultrastructural analysis revealed that CART establishes axosomatic and axodendritic contacts with CRH neurons in the PVN. These data demonstrate a selective effect of CART to phosphorylate CREB in CRH, but not TRH neurons in the PVN. Since CART is capable of increasing the gene expression of both CRH and TRH in hypophysiotropic neurons, and CART-containing axon terminals establish synaptic relationships with hypophysiotropic CRH and TRH neurons, we propose that CART may signal to the nucleus by more than one pathway.
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PMID:Central administration of cocaine- and amphetamine-regulated transcript increases phosphorylation of cAMP response element binding protein in corticotropin-releasing hormone-producing neurons but not in prothyrotropin-releasing hormone-producing neurons in the hypothalamic paraventricular nucleus. 1475 97

Cocaine- and amphetamine-regulated transcript (CART) was originally isolated from rat brain, but CART is also synthesized and stored in the anterior pituitary. The localization of pituitary CART and factors regulating its synthesis are largely unknown. The regulation of pituitary CART synthesis and release in response to CRH and glucocorticoids was examined in vitro and in vivo. CART immunoreactivity (CART-IR) was released from anterior pituitary segments. This release was increased 15-fold in response to corticotropin-releasing hormone (CRH). Intraperitoneal administration of CRH to rats significantly increased plasma CART-IR. Furthermore, CART-IR content and plasma CART-IR were significantly increased in adrenalectomized rats, and anterior pituitary CART mRNA expression, CART-IR content, and plasma CART-IR were significantly decreased in corticosterone-treated rats. Plasma CART-IR showed a pattern of diurnal variation similar to that of ACTH and corticosterone, and plasma CART-IR was positively correlated with corticosterone. CART-IR was detectable in the medium of the corticotroph cell line AtT-20. Dual in situ hybridization for prepro-CART (ppCART) mRNA expression and immunocytochemistry for ACTH showed localization of ppCART mRNA to a subpopulation of ACTH-immunoreactive cells. These findings demonstrate that pituitary CART expression and release are regulated by CRH and the glucocorticoid environment and that pituitary CART is partly localized to corticotrophs.
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PMID:Regulation of rat pituitary cocaine- and amphetamine-regulated transcript (CART) by CRH and glucocorticoids. 1513 56

Cocaine produces characteristic behavioral and autonomic responses due to its unique pharmacological properties. Many of the autonomic responses resemble those to acute behavioral stress. Both cocaine and behavioral stress have been shown to evoke an increase in sympathetic nerve activity that is primarily responsible for the peripheral cardiovascular responses. We noted varying hemodynamic and sympathetic response patterns to cocaine administration and to acute behavioral stress in rats that correlate with the predisposition to develop both a sustained increase in arterial pressure and cardiomyopathies. Several lines of evidence suggest that the autonomic response patterns are dependent on the actions of central peptides including angiotensin II (Ang II) and corticotropin-releasing hormone (CRH). This is based on observations demonstrating that intracerebroventricular (icv) administration of receptor antagonists for Ang II or CRH attenuated the decrease in cardiac output (CO) and increase in vascular resistance noted in some animals after cocaine administration or startle. In contrast, icv Ang II enhances the cardiodepression associated with cocaine administration or startle. Based on this and other evidence, we propose that the autonomic response patterns to startle and to cocaine are closely related and dependent on central Ang II and CRH. Furthermore, we suggest that these central peptides may be responsible for varying predisposition to cardiovascular disease.
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PMID:Role of angiotensin II and corticotropin-releasing hormone in hemodynamic responses to cocaine and stress. 1568 Apr 64

The present study explores the role of beta-endorphin-producing neurons of the arcuate nucleus in the behavioral effects of cocaine (i.e. acquisition of cocaine self-administration). Eight-week-old female rats were treated with a single estradiol valerate injection that causes a progressive lesion that is specific to beta-endorphin-producing neurons throughout the arcuate nucleus. Cocaine acquisition was suppressed following estradiol valerate pretreatment, while water reinforced behavior was similar to controls. Since estradiol valerate treated rats exhibit low estrogen plasma levels, estrogen replacement was performed but cocaine self-administration acquisition remained suppressed. In addition, analysis of beta-endorphin, dopamine, and DOPAC tissue levels confirmed the specificity of the endorphinic lesion resulting from estradiol valerate treatment. The suppression of cocaine self-administration acquisition following estradiol valerate treatment provides evidence for a significant role for beta-endorphin in cocaine reward.
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PMID:A hypothalamic endorphinic lesion attenuates acquisition of cocaine self-administration in the rat. 1604 29

Cocaine- and amphetamine regulated transcript (CART) is a recently discovered anorexigenic peptide, widely expressed in the central nervous system. Included among presumed hypothalamic mediated functions of CART are inhibition of food intake, stimulation of energy expenditure and regulation of hypothalamic-pituitary axes. CART-immunoreactive (IR) axons densely innervate the majority of hypophysiotropic thyrotropin-releasing hormone-(TRH) containing neurons in the hypothalamic paraventricular nucleus (PVN) and establish asymmetric synaptic specializations with the TRH neurons. The CART-IR innervation of TRH neurons originates from at least two major sources: CART neurons in the arcuate nucleus that co-express the anorexigenic peptide, alpha-melanocyte-stimulating hormone (alpha-MSH), and adrenergic CART neurons in the medulla. Based on the origins of the CART innervation and potent stimulatory effects of CART on TRH gene expression of hypophysiotropic neurons, CART is suggested to be involved in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis by different physiological stimuli. This regulatory control may contribute to the effects of fasting and cold exposure to reset the set point for feedback regulation of hypophysiotropic TRH gene expression and hence, affect circulating thyroid hormone levels. In addition, CART is present in the majority of hypophysiotropic TRH neurons and in TRH-containing axon terminals adjacent to the capillary vessels in the median eminence. While CART, alone, has no effect on the TSH and prolactin secretion from anterior pituitary cells, CART inhibits the stimulatory effect of TRH on prolactin secretion, but has no effect on TRH-induced increase of TSH release. Co-secretion of CART with TRH into the portal pituitary circulation, therefore, may have an important modulatory influence on the effect of TRH on pituitary hormone secretion.
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PMID:Neuroendocrine implications for the association between cocaine- and amphetamine regulated transcript (CART) and hypophysiotropic thyrotropin-releasing hormone (TRH). 1673 Aug 60

Cocaine and amphetamine-regulated transcript (CART) peptides are suggested to play a role in several physiological processes including feeding, reward, neuroendocrine modulation, and the stress response. Although some studies implicate the modulation of CART peptide expression by glucocorticoids, direct evidence relating CART to the stress response is limited. The present study was undertaken to evaluate the possible involvement of CART peptides during acute stress in male and female rats. Forced swim was used as the stress procedure. Following stress, serum adrenocorticotropic hormone (ACTH), and corticosterone (CORT) levels were determined, and CART immunocytochemistry was performed in the paraventricular (PVN) and arcuate (ARC) nuclei of the hypothalamus. Our results depict the following changes: (1) Serum ACTH and CORT levels were increased by stress and CORT levels were higher in female rats than males. (2) Stress modulated the number of CART expressing neurons. The degree and direction of this modulation varied according to the hypothalamic region and the sex of the subject. Forced swim stress increased CART peptide expression significantly in the PVN of female rats. In males, although there was a tendency for an increase in CART-immunoreactive cells by forced swim stress, the difference was not statistically significant. In the ARC nucleus, forced swim stress did not affect CART peptide expression in either sex. Our results suggest differential and sexually dimorphic modulation of CART expression in the PVN and ARC by forced swim stress.
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PMID:Sex differences in the regulation of cocaine and amphetamine-regulated transcript expression in hypothalamic nuclei of rats by forced swim stress. 1744 58

Cocaine- and amphetamine-regulated transcript (CART) is a recently discovered anorexigenic peptide. In rodents, CART inhibits food intake and is expressed in the anorexigenic alpha-MSH- but not in the orexigenic neuropeptide Y (NPY)- and agouti-related protein (AGRP)-synthesizing neurons of the arcuate nucleus. To understand whether CART is similarly expressed in feeding-related neuronal groups of the human hypothalamus as observed in rodents, colocalization of CART with alpha-MSH, NPY, AGRP, and melanin-concentrating hormone was studied using double-labeling immunofluorescence and confocal microscopy on human hypothalamic tissues obtained at autopsy. Unlike in rodents, we observed that CART is absent from the perikarya and axons of alpha-MSH-synthesizing neurons, but expressed in approximately one third of NPY/AGRP neurons in the human infundibular nucleus. In the lateral hypothalamus of the humans, colocalization of CART and melanin-concentrating hormone was observed, similar to that described in rodents. The anatomy of CART-containing neurons in the human infundibular nucleus differs markedly from that observed in the rodent brain, raising the question whether the colocalization of CART with orexigenic NPY and AGRP neurons is associated with an orexigenic role of CART in the human brain.
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PMID:Cocaine- and amphetamine-regulated transcript (CART) is colocalized with the orexigenic neuropeptide Y and agouti-related protein and absent from the anorexigenic alpha-melanocyte-stimulating hormone neurons in the infundibular nucleus of the human hypothalamus. 1752 22

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