Beth Tannenbaum

Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r's > -0.6). These findings suggest that maternal behavior serves to "program" hypothalamic-pituitary-adrenal responses to stress in the offspring.

The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.

High-fat feeding induces insulin resistance and increases the risk for the development of diabetes and coronary artery disease. Glucocorticoids exacerbate this hyperinsulinemic state, rendering an individual at further risk for chronic disease. The present studies were undertaken to determine whether dietary fat-induced increases in corticosterone (B) reflect alterations in the regulatory components of the hypothalamic-pituitary-adrenal (HPA) axis. Adult male rats were maintained on a high-fat (20%) or control (4%) diet for varying periods of time. Marked elevations in light-phase spontaneous basal B levels were evident as early as 7 days after fat diet onset, and B concentrations remained significantly elevated up to 21 days after fat diet onset compared with controls. In contrast, there were no significant effects on any parameters of spontaneous growth hormone secretory profiles, thus providing support for the specificity of the effects on the HPA axis. In a second study, all groups of rats fed the high-fat diet for 1, 9, or 12 wk exhibited significantly elevated levels of plasma adrenocorticotropic hormone, B, fatty acid, and glucose before, during, and/or at 20, 60, and/or 120 min after the termination of a restraint stress. Furthermore 12-wk fat-fed animals showed a significant resistance to insulin compared with normally fed controls. There were no differences in negative feedback efficacy in high-fat-fed rats vs. controls. Taken together, these results suggest that dietary fat intake acts as a background form of chronic stress, elevating basal B levels and enhancing HPA responses to stress.