Corticotropin‐releasing factor (<scp>CRF</scp>) receptor‐1 is involved in cardiac noradrenergic activity observed during naloxone‐precipitated morphine withdrawal

Martínez-Laorden, Elena; García-Carmona, Juan-Antonio; Baroja‐Mazo, Alberto; Romecín, Paola; Atucha, Noemı́ M.; Milanés, M. Victoria; Laorden, María‐Luisa

doi:10.1111/bph.12511

Cited by 13 publications

(5 citation statements)

References 62 publications

(69 reference statements)

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“…According to previous data obtained in rats treated chronically with morphine, another drug of abuse [ 54 – 56 ], present results demonstrated an increase in HSP27 expression and phosphorylation in mice exposed to ethanol or MDMA; these effects were potentiated when the combination of both drugs was used. While HSP27 can block actin polymerization, the phosphorylation of HSP27 is related to re-organization of the actin-based cytoskeletal structures [ 57 ].…”

Section: Discussionsupporting

confidence: 84%

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

et al. 2015

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Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone.

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Section: Discussionsupporting

confidence: 84%

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

et al. 2015

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“…This pattern of morphine administration, which involves ascending drug doses, has been used extensively to study opioid tolerance and dependence [ 26 – 29 ]. The doses of morphine were selected based in previous studies from our laboratory performed in CRF1R knockout mice [ 30 , 31 ]. The chronic saline-treated groups were administered with saline (i.p.)…”

Section: Methodsmentioning

confidence: 99%

Sex Differences between CRF1 Receptor Deficient Mice following Naloxone-Precipitated Morphine Withdrawal in a Conditioned Place Aversion Paradigm: Implication of HPA Axis

et al. 2015

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BackgroundExtinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R) and the different response of male and female mice in the expression and extinction of the aversive memory.Methodology/Principal FindingWe used genetically engineered male and female mice lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection of increasing doses of morphine (10–60 mg/kg). Negative state associated with naloxone (1 mg/kg s.c.)-precipitated morphine withdrawal was examined by using conditioned place aversion (CPA) paradigm. No sex differences for CPA expression were found in wild-type (n = 29) or CRF1R knockout (KO) mice (n = 29). However, CRF1R KO mice presented less aversion score than wild-type mice, suggesting that CRF1R KO mice were less responsive than wild-type to continuous associations between drug administration and environmental stimuli. In addition, CPA extinction was delayed in wild-type and CRF1R KO male mice compared with females of both genotypes. The genetic disruption of the CRF1R pathway decreased the period of extinction in males and females suggesting that CRF/CRF1R is implicated in the duration of aversive memory. Our results also showed that the increase in adrenocorticotropic hormone (ACTH) levels observed in wild-type (n = 11) mice after CPA expression, were attenuated in CRF1R KO mice (n = 10). In addition, ACTH returned to the baseline levels in males and females once CPA extinction was finished.Conclusion/SignificanceThese results suggest that, at least, CPA expression is partially due to an increase in plasma ACTH levels, through activation of CRF1R, which can return when CPA extinction is finished.

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“…Both of them are expressed in the central nervous system 2 13 14 and periphery 2 15 and mediate cardiovascular effects of the CRF system. In CRFR1 knockout mice, an abnormally high cardiac noradrenergic activity following stress induced by morphine withdrawal, which is observed on wildtype mice, is inhibited 16 . Moreover, systemic administration of urocortin 1 fails to decrease MAP in CRFR2 knockout mice, whereas wildtype mice show a marked reduction 17 18 .…”

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confidence: 97%

Corticotropin releasing factor excites neurons of posterior hypothalamic nucleus to produce tachycardia in rats

Gao

Zhuang

et al. 2016

Sci Rep

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Corticotropin releasing factor (CRF), a peptide hormone involved in the stress response, holds a key position in cardiovascular regulation. Here, we report that the central effect of CRF on cardiovascular activities is mediated by the posterior hypothalamic nucleus (PH), an important structure responsible for stress-induced cardiovascular changes. Our present results demonstrate that CRF directly excites PH neurons via two CRF receptors, CRFR1 and CRFR2, and consequently increases heart rate (HR) rather than the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). Bilateral vagotomy does not influence the tachycardia response to microinjection of CRF into the PH, while β adrenergic receptor antagonist propranolol almost totally abolishes the tachycardia. Furthermore, microinjecting CRF into the PH primarily increases neuronal activity of the rostral ventrolateral medulla (RVLM) and rostral ventromedial medulla (RVMM), but does not influence that of the dorsal motor nucleus of the vagus nerve (DMNV). These findings suggest that the PH is a critical target for central CRF system in regulation of cardiac activity and the PH-RVLM/RVMM-cardiac sympathetic nerve pathways, rather than PH-DMNV-vagus pathway, may contribute to the CRF-induced tachycardia.

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Corticotropin‐releasing factor (CRF) receptor‐1 is involved in cardiac noradrenergic activity observed during naloxone‐precipitated morphine withdrawal

Cited by 13 publications

References 62 publications

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

Sex Differences between CRF1 Receptor Deficient Mice following Naloxone-Precipitated Morphine Withdrawal in a Conditioned Place Aversion Paradigm: Implication of HPA Axis

Corticotropin releasing factor excites neurons of posterior hypothalamic nucleus to produce tachycardia in rats

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