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.