DEXAMETHASONE RESISTANCE AMONG NONHUMAN-PRIMATES ASSOCIATED WITH A SELECTIVE DECREASE OF GLUCOCORTICOID RECEPTORS IN THE HIPPOCAMPUS AND A HISTORY OF SOCIAL INSTABILITY

We have studied some of the neuroendocrine and social correlates of de xamethasone resistance in a nonhuman primate population. Subjects were 51 male Macaca fascicularis monkeys with known behavioral histories a nd who had been given dexamethasone (DEX) suppression tests a week pri or to killing. We compared the subset of monkeys who were most DEX res ponsive (post-DEX cortisol values of 3.1 +/- 0.5 mu g/dl) versus a DEX -resistant subset (cortisol values of 9.2 +/- 2.0 mu g/dl); we found t wo features that distinguished these groups: (a) DEX-resistant monkeys had significantly fewer available glucocorticoid receptor (GR) bindin g sites in the hippocampus; they did not differ in numbers of mineralo corticoid receptor (MR) sites in the hippocampus, nor in numbers for e ither receptor in the cortex or hypothalamus as a whole. (b) Animals h ad resided for a number of years in social groups that were either sta ble or were repeatedly destabilized by changing of group membership; t he latter has been shown to constitute a sustained stressor. DEX-resis tant animals were more than twice as likely to have come from an unsta ble group as were DEX-responsive monkeys. Rodent studies have shown th at sustained stress can cause a selective downregulatory decrease in t he numbers of hippocampal corticosteroid receptors, and that such a lo ss is associated with DEX resistance. The present data suggest similar associations in the primate, and may be of relevance to the DEX resis tance observed in a subset of human depressives.