Heroin-induced alterations in leukocyte numbers and apoptosis in the rat spleen

The present study assessed the effects of acute heroin treatment on the cel lularity of the rat spleen and the rate of splenocyte death by necrosis or apoptosis. The results showed that 1 h after a single injection of heroin, the total number of leukocytes in the spleen was decreased in a dose-depend ent manner. Prior injection of naltrexone completely blocked heroin's effec t, and the heroin-induced decrease in splenic leukocytes was not associated with a heroin-induced increase in circulating leukocytes. A 1-h exposure t o heroin did not increase levels of lactate dehydrogenase, a cytosolic enzy me, in supernatants of splenic mononuclear cells cultured for 45 min or 24 h, suggesting that heroin does not increase necrotic death in the spleen. I n contrast, a 1-h heroin treatment did increase the percentage of Annexin V + cells in 0- and 24-h cultures of splenic mononuclear cells, indicating th at heroin increases apoptotic death in the spleen, A 3-h exposure to heroin also produced a significant increase in apoptosis in the spleen. DNA fragm entation, a marker of cells in late stages of apoptosis, could not be detec ted in fresh splenocytes, but was evident in 24-h cultures of splenic monon uclear cells from saline- and heroin-treated rats. These results demonstrat e that a single administration of heroin produces a decrease in the number of splenic leukocytes and an increase in the apoptotic death of splenic mon onuclear cells. (C) 2000 Academic Press.