Publication: Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor
Authors
Navarro Zaragoza, Javier ; Martínez Laorden, Elena ; Mora, L. ; Hidalgo, J. ; Laorden Carrasco, María Luisa ; Milanés Maquilón, María Victoria
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Publisher
Elsevier
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DOI
https://doi.org/10.1016/j.taap.2013.12.021
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info:eu-repo/semantics/article
Description
Abstract
Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts.
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Citation
Toxicology and Applied Pharmacology 275 (2014) 28–35
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