title: Changes in c-fos expression in the rat heart during morphine withdrawal. Involvement of alpha2-adrenoceptors.
abstract: We previously demonstrated an increase in Fos expression in the heart during morphine withdrawal. In the present study we examined the role of beta- and alpha-adrenoceptors in naloxone-precipitated increases in Fos expression in the heart. Dependence on morphine was induced by 7-day chronic subcutaneous implantation of six morphine pellets (75 mg). Morphine withdrawal was precipitated by administration of naloxone (5 mg/kg subcutaneously) on day 8. Using immunohistochemical staining of Fos, the present results indicate that morphine withdrawal induced marked Fos immunoreactivity (Fos-IR) within the cardiomyocyte nuclei. Moreover, Western blot analysis revealed a peak expression of c-fos in the right and left ventricles after naloxone-precipitated withdrawal in parallel with an increase in noradrenaline (NA) turnover. In the second study, the effects of the administration of adrenoceptor antagonists on withdrawal-induced Fos expression in the heart were studied. Pretreatment with the beta antagonist, propranolol (3 mg/kg intraperitoneally) or alpha1-adrenoceptor antagonist, prazosin (1 mg/kg intraperitoneally) did not block the marked Fos-IR or the hyperactivity of catecholaminergic neurons observed in the heart during withdrawal. However, pre-treatment with alpha2-adrenoceptor antagonist, yohimbine (1 mg/kg intraperitoneally), 20 min before naloxone administration to morphine-dependent rats antagonized Fos expression and the enhancement of NA turnover in the heart. Collectively, these results suggest that noradrenergic neurons in the heart are active during morphine withdrawal, and that activation of transcriptional responses mediated by Fos are dependent upon cardiac alpha2-adrenoceptor.
authors.affiliation: Equip of Cellular and Molecular Pharmacology, University School of Medicine, Murcia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: González-Cuello
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Milanés
authors.forename: Manuel
authors.initials: M
authors.lastname: Aviles
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Laorden
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D016762:Genes, fos / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009270:Naloxone / Q000378:metabolism / Q000494:pharmacology; D009647:Normetanephrine / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D015016:Yohimbine / Q000378:metabolism / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D009647:Normetanephrine; D015016:Yohimbine; D009270:Naloxone; D009020:Morphine; D011433:Propranolol; D011224:Prazosin