GLOBAL SEX-DIFFERENCES IN STRESS-INDUCED ACTIVATION OF CEREBRAL METABOLISM REVEALED BY 2-DEOXYGLUCOSE AUTORADIOGRAPHY

Although it is well known that there are sex differences in stress-ind uced activation of the hypothalamic-pituitary-adrenal axis, it is not known if there are also gender-related differences in stress-induced n eural activity. In this study, restraint and formalin injections into a forelimb were used as stressors and 2-[C-14]deoxyglucose (2DG) autor adiography was used to evaluate regional brain glucose metabolism, an index of neural activity. Analysis of blood samples collected during t he 2DG procedure confirmed that stress elevates plasma glucose levels significantly more in females than in males. Moreover, females show hi gher brain glucose utilization in all regions examined, including sex hormone-responsive regions such as the medial amygdala, medial preopti c nucleus, ventromedial nucleus, and arcuate nucleus, as well as the C A1 layer and dentate region of the hippocampus, the posterior parietal (sensorimotor) cortex, medial and lateral habenula, and splenium of t he corpus callosum. The sex differences are apparent regardless of whe ther animals were injected with saline or formalin. Interestingly, the medial preoptic area, which shows robust neuroanatomical sex differen ces, demonstrates greater activation in response to formalin than to s aline only in females. In some regions of both males and females, gluc ose utilization was higher on the side of the brain contralateral to t he saline or formalin injection site. These findings suggest that ther e are widespread, gender-related differences in neuronal as well as en docrine activation in response to highly stressful conditions. (C) 199 6 Academic Press.