Chronic morphine induces up-regulation of the pro-apoptotic Fas receptor and down-regulation of the anti-apoptotic Bcl-2 oncoprotein in rat brain

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dc.contributor.author Boronat, M. A.
dc.contributor.author García-Fuster, M. J.
dc.contributor.author García-Sevilla, J. A.
dc.date.accessioned 2020-01-09T08:51:47Z
dc.date.available 2020-01-09T08:51:47Z
dc.identifier.uri http://hdl.handle.net/11201/150533
dc.description.abstract [eng] This study was designed to assess the influence of activation and blockade of the endogenous opioid system in the brain on two key proteins involved in the regulation of programmed cell death: the pro‐apoptotic Fas receptor and the anti‐apoptotic Bcl‐2 oncoprotein. The acute treatment of rats with the μ‐opioid receptor agonist morphine (3 - 30 mg kg−1, i.p., 2 h) did not modify the immunodensity of Fas or Bcl‐2 proteins in the cerebral cortex. Similarly, the acute treatment with low and high doses of the antagonist naloxone (1 and 100 mg kg−1, i.p., 2 h) did not alter Fas or Bcl‐2 protein expression in brain cortex. These results discounted a tonic regulation through opioid receptors on Fas and Bcl‐2 proteins in rat brain. Chronic morphine (10 - 100 mg kg−1, 5 days, and 10 mg kg−1, 13 days) induced marked increases (47 - 123%) in the immunodensity of Fas receptor in the cerebral cortex. In contrast, chronic morphine (5 and 13 days) decreased the immunodensity of Bcl‐2 protein (15 - 30%) in brain cortex. Chronic naloxone (10 mg kg−1, 13 days) did not alter the immunodensities of Fas and Bcl‐2 proteins in the cerebral cortex. The concurrent chronic treatment (13 days) of naloxone (10 mg kg−1) and morphine (10 mg kg−1) completely prevented the morphine‐induced increase in Fas receptor and decrease in Bcl‐2 protein immunoreactivities in the cerebral cortex. The results indicate that morphine, through the sustained activation of opioid receptors, can promote abnormal programmed cell death by enhancing the expression of pro‐apoptotic Fas receptor protein and damping the expression of anti‐apoptotic Bcl‐2 oncoprotein.
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dc.relation.isformatof Versió postprint del document publicat a: https://doi.org/10.1038/sj.bjp.0704364
dc.relation.ispartof British Journal of Pharmacology, 2001, vol. 134, num. 6, p. 1263-1270
dc.rights (c) The British Pharmacological Society, 2001
dc.subject.classification 615 - Farmacologia. Terapèutica. Toxicologia. Radiologia
dc.subject.other 615 - Pharmacology. Therapeutics. Toxicology
dc.title Chronic morphine induces up-regulation of the pro-apoptotic Fas receptor and down-regulation of the anti-apoptotic Bcl-2 oncoprotein in rat brain
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion
dc.date.updated 2020-01-09T08:51:47Z
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.identifier.doi https://doi.org/10.1038/sj.bjp.0704364


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