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)

The neuropeptide, corticotropin-releasing hormone (CRH), has been shown to play a role in behavioral and neurobiological effects of drugs of abuse. An important modulator of CRH, the CRH binding protein (CRH-BP), has not, on the other hand, been assessed for its role in drug-associated effects. The primary objective of the present experiment was to assess whether prior, chronic exposure to cocaine modulates expression of CRH-BP, and to compare expression of the BP with that of the peptide itself. We assessed CRH-BP and CRH mRNA expression in two brain regions where CRH is known to affect responses to drugs of abuse; namely, the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST). Male Long-Evans rats were given 14 daily injections of cocaine (30 mg/kg, i.p.) or saline. One, 3, 10, 28, or 42 days post-treatment, animals were killed and adjacent brain sections through the CeA and BNST were processed for CRH-BP and CRH by in situ hybridization. In the CeA, cocaine pre-exposure increased both CRH and CRH-BP mRNA expression 1 day post-treatment. In the dorsal BNST, cocaine pre-exposure elevated levels of CRH-BP, but not CRH, mRNA 3 days post-treatment. Taken together, the results suggest that withdrawal-induced changes in the expression of the CRH-BP, and CRH itself, are relatively short-lived and that a dysregulation in basal expression of either gene is not likely responsible for long-lasting behavioral effects noted with cocaine and other drugs of abuse.
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PMID:Effects of chronic cocaine exposure on corticotropin-releasing hormone binding protein in the central nucleus of the amygdala and bed nucleus of the stria terminalis. 1475 Dec 91

Gender and genotype result in differential sensitivity to stress and to nicotine. Male and female Sprague-Dawley and Long-Evans rats exhibit different behavioral responses to immobilization stress and to chronically-administered nicotine, suggesting that these animals may be useful to model human variability in stress and nicotine sensitivity. It is possible that differences in sensitivity of the hypothalamo-pituitary-adrenocortical (HPA) axis might account for these sex and strain differences. This experiment examined corticosterone (CORT) and adrenocorticotropin hormone (ACTH) responses of male and female Sprague-Dawley (n=117) and Long-Evans (n=120) rats administered 0, 6, or 12 mg/kg/day nicotine for 14 days; half of each treatment group was exposed to immobilization stress (20 min/day). Feeding and body weight also were measured. Nicotine increased CORT and ACTH levels of Sprague-Dawley females only. Stress increased CORT and ACTH levels of all groups except for Long-Evans females. Nicotine and stress decreased feeding and body weight with greatest effects in Long-Evans females. CORT, feeding, and body weight were positively correlated among stressed females. These findings suggest that strain differences in HPA axis, body weight, and feeding responses to nicotine and to stress are robust among females but not among males. CORT reactivity and female sex hormones may explain these differences.
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PMID:Strain and sex alter effects of stress and nicotine on feeding, body weight, and HPA axis hormones. 1582 May 27

Peptide S (NPS or PEPS) and its cognate receptor have been recently identified both in the central nervous system and in the periphery. NPS/PEPS promotes arousal and has potent anxiolytic-like effects when it is injected centrally in mice. In the present experiment, we tested by different approaches its central effects on feeding behaviour in Long-Evans rats. PEPS at doses of 1 and 10 microg injected in the lateral brain ventricle strongly inhibited by more than 50% chow intake in overnight fasted rats with effects of longer duration with the highest dose (P<0.0001). A similar decrease was observed for the spontaneous intake of a high-energy palatable diet (-48%; P<0.0001). This anorexigenic effect was comparable to that induced by corticotropin-releasing hormone in fasted rats at equimolar doses. However, peptide S did not modify food intake stimulated by neuropeptide Y (NPY) at equimolar doses. It also did not affect the fasting concentrations of important modulators of food intake like leptin, ghrelin, and insulin in circulation. This study therefore showed that peptide S is a new potent anorexigenic agent when centrally injected. Its inhibitory action appears to be independent of the NPY, ghrelin, and leptin pathways. Development of peptide S agonists could constitute a new approach for the treatment of obesity.
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PMID:Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats. 1591 54

This study used a rat model of Fetal Alcohol Syndrome to investigate whether combined prenatal and postnatal ethanol exposure affects met-enkephalin levels in the brains of male and female Long-Evans adult rats. Intragastric ethanol was administered to a group of rats (ET) from gestational day (GD) 1 through 22 and from postnatal day (PD) 2 through 10. The control groups consisted of a nontreated control group (NTC) and an intubated control group (IC) that received the intragastric intubation procedure but no exposure to ethanol. We measured met-enkephalin levels in the prefrontal cortex, nucleus accumbens, hypothalamus, central and basolateral nucleus of amygdala and ventral tegmental area. Met-enkephalin levels in the hypothalamus of male and female ET animals were significantly higher than those in either the NTC or IC animals. Met-enkephalin levels in the central nucleus of the amygdala of male and female ET animals were significantly lower than the levels in the NTC animals. Met-enkephalin levels in the nucleus accumbens of ET females were significantly greater than those in the IC females. These results demonstrate that the combination of prenatal and postnatal ethanol exposure affects basal met-enkephalin levels in specific regions in a sex-specific manner. These changes in met-enkephalin levels may explain how early ethanol exposure affects opioid-regulated behaviors such as social play, sexual behavior, and other social behaviors.
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PMID:Perinatal ethanol exposure alters met-enkephalin levels of male and female rats. 1645 85

Urocortin (UCN), a newly identified, 40-amino-acid, corticotropin-releasing hormone (CRH) structurally related peptide, has been demonstrated to be expressed in the central nervous system and many peripheral tissues of rats and man. This study aimed to investigate the expression profile of UCN in rat lung and the effect of UCN on lung vascular permeability. The expression of UCN mRNA was detected by reverse transcriptase PCR (RT-PCR). UCN peptide was measured by immunohistochemistry and Western blot analysis. We found that both UCN mRNA and peptide were obviously expressed in rat lung. Immunohistochemistry results showed that UCN peptide is mainly expressed in bronchial epithelium mucosa and alveolar epithelium. We also found that rats receiving inhalation aerosol of UCN had a significant elevation of lung vascular permeability compared with rats receiving vehicle and ovalbumin (OVA) by the Evans blue (EB) technique. UCN aerosol inhalation resulted in obvious pulmonary congestion and edema observed under light microscope by hematoxylin and eosin (HE) staining. The nonselective peptide CRH receptor antagonist astressin markedly reduced lung vascular permeability triggered by UCN. Enhanced pulmonary vascular permeability induced by UCN was markedly inhibited by pretreatment with the mast-cell stabilizer cromolyn and histamine-1 (H1) receptor antagonist azelastine respectively, but not by the leukotriene receptor antagonist montelukast. In summary, in the present study, we demonstrated for the first time that UCN is expressed in rat lung and contributes to an increase in lung vascular permeability through activation of CRH receptors. Mast cells and histamine may be involved in this effect of UCN. Peripherally produced UCN in lung may act as an autocrine and paracrine proinflammatory factor.
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PMID:Expression of urocortin in rat lung and its effect on pulmonary vascular permeability. 1661 91

Neonatal maternal separation (MS) has been used to model long-term changes in neurochemistry and behaviour associated with exposure to early-life stress. This study characterises changes in behavioural and neuroendocrine parameters following MS. On postnatal days (PND) 3-15, male and female Long-Evans rats underwent 3 h daily MS. Non-handled (NH) control offspring remained with the dams. Starting at PND 90, behaviour was assessed at weekly intervals in the elevated plus-maze, elevated T-maze, and locomotor activity boxes, and body weight monitored throughout. At the end of the study, adrenals were weighed and blood collected for analysis of plasma corticosterone and adrenocorticotropic hormone (ACTH) under basal conditions and following restraint stress. As adults, MS weighed more than NH animals. Activity on the open arms of the plus-maze was similar between MS and NH animals. In the T-maze, MS males had shorter emergence latencies than their NH counterparts. Spontaneous ambulation in a novel environment was significantly higher in MS than in NH animals, and males exhibited overall lower activity than females. Basal plasma corticosterone was lower in MS than in NH females, but no rearing condition difference was observed following restraint stress. Females had higher corticosterone and ACTH levels than males, whereas adrenal glands of MS animals weighed less than those of NH controls. The MS paradigm caused long-term gender dependent effects on behaviour and HPA axis status. The consistent gender differences confirm and expand existing results showing altered anxiety and stress reactivity in male and female rats.
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PMID:Long-lasting changes in behavioural and neuroendocrine indices in the rat following neonatal maternal separation: gender-dependent effects. 1673 Jun 78

Leptin, a hormone regulating body weight, food intake, and metabolism, is associated with activation of immune cells and inflammation. In this study we analyzed levels of leptin, adrenocorticotropic hormone (ACTH), corticosterone, interleukin 1beta (IL-1beta), and nitric oxide (NO) production on days 10 and 22 of adjuvant arthritis (AA) in male Long Evans rats to ascertain possible relationship of leptin with its modulators during the early and late phases of chronic inflammation. The circulating leptin levels were significantly reduced already on day 10 of AA compared to controls (1.97+/-0.22 ng/ml vs. 3.08+/-0.25 ng/ml, p<0.05); on day 22 no significant further drop was observed (1.06+/-0.21 ng/ml). Leptin mRNA in epididymal fat tissue was reduced in arthritic animals compared to controls on day 22 (0.61+/-0.09 vs. 1.30+/-0.1 arbU/GAPDH (p<0.01). IL-1beta concentration in spleen was enhanced on day 10 of AA (24.55+/-4.67 pg/100 microg protein vs. 14.33+/-1.71 pg/100 microg protein; p<0.05); on day 22 it did not differ from controls. ACTH and corticosterone levels were significantly elevated only on day 22 of AA (ACTH: 306.17+/-42.22 pg/ml vs. 157.61+/-23.94 pg/ml; p<0.05; corticosterone: 5.24+/-1.38 microg/100 ml vs. 1.05+/-0.23 microg/100 ml; p<0.01). Nitrate levels were enhanced similarly on days 10 (49.86+/-1.83 microM) and 22 of AA (43.58+/-2.17 microM), compared to controls (23.42+/-1.39 microM, p<0.001). These results show that corticosterone does not stimulate leptin production during AA. The suppression of leptin may be a consequence of permanent activation of NO, IL-1beta, and of lower weight gain. Circulating leptin does not seem to play a key role in the progression of chronic arthritis.
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PMID:Relationship among nitric oxide, leptin, ACTH, corticosterone, and IL-1beta, in the early and late phases of adjuvant arthritis in male Long Evans rats. 1696 44

In diabetes, dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis causes effects such as elevation of corticotropin (ACTH) and glucocorticoids. Cholecystokinin and its receptors are involved in the HPA axis and influence the regulation of the HPA axis. We examined adrenocortical function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, that lack the cholecystokinin A receptor. We measured adrenal weight, plasma ACTH, serum and urinary corticosterone, and serum leptin in OLETF rats at 5 to 36 weeks of age. Messenger RNA (mRNA) expression of 11beta-hydroxysteroid dehydrogenase and 5alpha-reductase type 1 in adrenal glands of the rats were examined. Long-Evans Tokushima Otsuka (LETO) rats were used as controls. In OLETF rats at 32 to 36 weeks of age, plasma ACTH was significantly higher (P < .001); serum corticosterone and 24-hour urinary corticosterone were significantly lower (P < .005); and adrenal weight was significantly lower (P < .005) than those in LETO rats. At the same ages, serum leptin in OLETF rats was significantly higher (P < .001) than that in LETO rats. In the younger OLETF rats, these changes were not observed. Overall, there was an inverse correlation between serum corticosterone and serum leptin (r = -0.374, P < .0005), whereas there was a positive correlation between plasma ACTH and serum leptin (r = 0.654, P < .0001). At 5 and 36 weeks of age, mRNA expression of 5alpha-reductase type 1 in the adrenal gland of OLETF rats was significantly higher (P < .05) than that of LETO rats, whereas there was no significant difference in mRNA expressions of 11beta-hydroxysteroid dehydrogenase types 1 and 2. We showed that adrenocortical insufficiency and adrenal atrophy were acquired in OLETF rats, and the possibility of elevated serum leptin relates to this phenomenon.
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PMID:Adrenocortical insufficiency in Otsuka Long-Evans Tokushima Fatty rats, a type 2 diabetes mellitus model. 1788 40

Hormones released in response to stress play important roles in cognition. In the present study, the effects of the stress peptide, corticotropin-releasing hormone (CRH), on spatial reference memory were assessed following post-training administration. Adult Long-Evans male rats were trained for 6 days on a standard water maze task of reference memory in which animals must learn and remember the fixed location of a hidden, submerged platform. Each day, immediately following three training trials, rats received bilateral infusions of CRH into the lateral ventricles over a range of doses (0.1, 0.33, 1.0, 3.3 microg) or a vehicle solution. Post-training infusions of CRH improved retention as indicated by significantly shorter latencies and path lengths to locate the hidden platform on the first training (retention) trial of days 2 and 3. Additionally, post-training administration of CRH increased spatial bias during probe trials as measured by proximity to the platform location. CRH did not enhance performance on retention or probe trials when administered 2h after daily training indicating that CRH facilitated consolidation specifically. The effects of CRH were attenuated by intraventricular co-administration of the beta-adrenergic antagonist, propanolol, at bilateral doses that had no effect on retention alone (0.1, 1.0 microg). Results indicate that post-training administration of CRH enhanced spatial memory as measured in a water maze, and this effect was mediated, at least partly, by a noradrenergic mechanism.
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PMID:Post-training administration of corticotropin-releasing hormone (CRH) enhances retention of a spatial memory through a noradrenergic mechanism in male rats. 1808 39

Abstract Previous studies have shown that microinjection of cytotoxic lgG2a monoclonal antibody to rat/human corticotropin-releasing factor (CRF-MAb) into the hypothalamic paraventricular nucleus of Long Evans rats resulted in antibody uptake into specific neurons of the paraventricular nucleus. We tested the hypothesis that this neuronal uptake may allow non-linked toxins to enter into specific neurons. The effects of central or peripheral administration of a mix containing CRF-MAb and cellular toxins (toxin/ CRF-MAb) on plasma adrenocorticotropin levels were determined before and after exposure to ether stress in freely moving rats. Peripheral injection (jugular vein) of the toxin/CRF-MAb mix or injection into the supraoptic nuclei did not affect resting or stress-induced adrenocorticotropin secretion. In contrast, bilateral injection of the same mix into the paraventricular nucleus or the lateral ventricle caused a consistent 70% reduction of the ether stress-induced adrenocorticotropin release but had no significant effect on the resting adrenocorticotropin levels. The blocking effect of intracerebroventricular administration disappeared after 24 h whereas the blockade persisted for at least 15 days after local injection into the paraventricular nucleus. The injection into the paraventricular nucleus of CRF-MAb without toxins restricted the inhibitory effects to 24 h. These data suggest that administration of a mix of toxins added to a specific lgG2a monoclonal antibody to CRF resulted in a long-term interference with the control of adrenocorticotropin secretion. This new approach may be of use for elucidating the physiological roles of different central peptidergic systems.
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PMID:Long-term inhibition of stress-induced adrenocorticotropin release by intracerebral administration of a monoclonal antibody to rat corticotropin-releasing factor together with ricin a chain and monensin. 1921 94


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