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Naunyn Schmiedebergs Arch Pharmacol. 2003 Nov;368(5):421-31. Epub 2003 Oct 3.

Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain.

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  • 1Laboratory of Neuropharmacology, Associate Unit of the Institute of Neurobiology "Ramón y Cajal" (CSIC), Department of Biology, University of the Balearic Islands, Cra. Valldemossa Km 7.5, 07122, Palma de Mallorca, Spain.


The Fas receptor is involved in the regulation of apoptosis but also can function as a non-apoptotic signal transducer. This study was mainly designed to quantitate Fas proteins in rat brain during heroin addiction and opiate withdrawal. In rat, mouse and human brains, and in SH-SY5Y cells, similar forms of Fas were immunodetected with different antibodies (i.e., 35 kDa native Fas and 48- and 51-kDa glycosylated Fas). Acute (2 h) treatments with the micro-opioid receptor agonists heroin (10 mg/kg) and morphine (30 mg/kg) increased the immunodensity of native Fas (124% and 36%) but not that of glycosylated Fas in the cerebral cortex. Chronic (5 days) heroin (5-30 mg/kg) and morphine (10-100 mg/kg) were also associated with increased native Fas (76% and 45%) and with different expressions of glycosylated Fas. In heroin-dependent rats, opiate withdrawal (48 h) resulted in a sustained increase in native Fas (107%) and in up-regulation of 51 kDa glycosylated Fas (51%). Acute treatments with selective delta-receptor (SNC-80, 10 mg/kg) or kappa-receptor (U 50488-H, 10 mg/kg) agonists did not alter the content of native or glycosylated Fas. Chronic pentazocine (10-80 mg/kg, 5 days), a mixed opiate drug and sigma(1) receptor agonist, decreased native (48%) and glycosylated (38-82%) Fas proteins. Similarly, the selective sigma(1) agonist (+)-SKF 10047 also decreased native Fas (37%) and the effect was blocked by the sigma(1) antagonist BD 1063. Brain dynamin was up-regulated by acute and/or chronic heroin (30-39%), morphine (47-85%), pentazocine (51%) and heroin withdrawal (74%). The main results indicate that chronic heroin/morphine treatment and heroin withdrawal are associated with up-regulation of 35 kDa native Fas (and with different expressions of glycosylated Fas), and also with concomitant increases of dynamin in rat brain.

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