The behavioral and neurochemical effects of an inescapable stressor are time of day dependent.

Circadian rhythms are ∼24 h fluctuations in physiology and behavior that are synchronized with the light-dark cycle. The circadian system ensures homeostatic balance by regulating multiple systems that respond to environmental stimuli including stress systems. In rats, acute exposure to a series of uncontrollable tailshocks (inescapable stress, IS) produces an anxiety and depression-like phenotype. Anxiety- and fear-related behavioral changes produced by IS are driven by sensitization of serotonergic (5-hydroxytryptamine, 5-HT) neurons in the dorsal raphe nucleus (DRN). Because the circadian and serotonergic systems are closely linked, here we tested whether the DRN-dependent behavioral and neurochemical effects of IS are time of day dependent. Exposure to IS during the light (inactive) phase elicited the expected changes in mood related behaviors. In contrast, rats that underwent IS during the dark (active) phase were buffered against stress-induced changes in juvenile social exploration and shock-elicited freezing, both DRN-dependent outcomes. Interestingly, behavioral anhedonia, which is not a DRN-dependent behavior, was comparably reduced by stress at both times of day. Neurochemical changes complimented the behavioral results: IS-induced activation of DRN 5-HT neurons was greater during the light phase compared to the dark phase. Additionally, 5-HT1AR and 5-HTT, two genes that regulate 5-HT activity were up-regulated during the middle of the light cycle. These data suggest that DRN-dependent behavioral outcomes of IS are time of day dependent and may be mediated by circadian gating of the DRN response to stress.Lay summaryHere we show that the time of day at which a stressor occurs impacts the behavioral and neurochemical outcomes of the stressor. In particular, animals appear more vulnerable to a stressor that occurs during their rest phase. This work may have important implications for shift-workers and other populations that are more likely to encounter stressors during their rest phase.

Age-related decline in social interaction is associated with decreased c-Fos induction in select brain regions independent of oxytocin receptor expression profiles.

Social behavior decreases with aging, and we have previously found a substantial decline in social investigative behavior of old female rats. In this study we examined the neural activation pattern (c-Fos mRNA) of young (3 month) and old (18 month) female rats after brief 10 min exposure to a novel female rat in order to identify forebrain regions that show selective age-related alterations in their neural response to social investigation. We also measured relative oxytocin receptor expression (Oxtr mRNA) as a possible factor in age-related declines in c-Fos induction after social interaction. Young rats exposed to a social partner had a greater c-Fos mRNA response than those exposed to novel context alone in the lateral septum and septohypothalamic area, with blunted increases evident in old rats. In addition, c-Fos mRNA levels in the lateral septum were positively correlated with social investigative behavior. Interestingly, age-related differences in c-Fos gene induction were unrelated to the local amount of Oxtr expression within specific brain regions, although we found an age-related decline in Oxtr expression in the ventromedial hypothalamus. This functional neuroanatomical characterization may point to certain brain regions that are especially sensitive to age-related declines associated with social interaction behavior.