Effects of streptozotocin-induced diabetes on neuronal sigma receptors in the rat brain

To study the effect of diabetes mellitus on the density of sigma receptors, in vitro binding experiments were conducted in whole brain homogenate memb ranes of 5-week and 10-week control rats and streptozotocin (STZ)-induced d iabetic rats. sigma-1 Receptors were labelled with [H-3](+)-pentazocine whi le sigma-2 receptors were labelled with [H-3] 1,3-di-o-tolylguanidine (DTG) in the presence of 0.5 mu M (+)-pentazocine to mask sigma-1 sites. Non-spe cific binding was determined in the presence of 20 mu M haloperidol. Scatch ard analysis revealed a 27% (p<0.01) decreased in sigma-1 receptor density and a 33% (p<0.01) decreased in sigma-2 receptor density in whole brain of 10-week STZ-diabetic rats. No statistically significant difference was foun d in the sigma receptor content of 5-week STZ-diabetic rats. These results provide evidence that neuronal sigma receptors are reduced in 10-week STZ-d iabetic rats and suggest that changes in sigma receptors may play a role in diabetes related abnormalities. Further evaluation is required to determin e whether changes observed in the brain are homogeneous for either or both sigma receptor subtypes as well as potential links between other CNS recept or changes previously observed in STZ-induced diabetic rats. (C) 1999 Elsev ier Science Inc.