Acute sleep deprivation enhances avoidance learning and spatial memory and induces delayed alterations in neurochemical expression of GR, TH, DRD1, pCREB and Ki67 in rats.

The current study investigated the effects of acute versus repeated periods of sleep deprivation on avoidance learning and spatial memory and on the expression of discrete biochemical brain signals involved in stress regulation, motivation and brain plasticity. Male Long-Evans rats were sleep deprived using the platform-over-water method for a single 4 h period (ASD) or for daily 4h RSD period on five consecutive days (CSD). The Y maze passive avoidance task (YM-PAT) and the Morris water maze (MWM) were used to determine learning and memory 1h following the last SD period. Region-specific changes in glucocorticoid receptors (GR), tyrosine hydroxylase (TH), dopamine 1 receptors (DRD1), phospho-CREB (pCREB) and Ki-67 expression were assessed in the hippocampal formation, hypothalamus and mesolimbic regions 72 h following RSD. Behaviorally, our findings revealed increased latency to re-enter the aversive arm in the YM-PAT and reduced distance traveled and latency to reach the platform in the MWM in ASD rats compared to all other groups, indicative of improved avoidance learning and spatial memory, respectively. Acute SD enhanced TH expression in the ventral tegmental area, nucleus accumbens and A11 neurons of the hypothalamus and DRD1 expression in the lateral hypothalamus. Cell proliferation in the subventricular zone and pCREB expression in the dentate gyrus and CA3 regions was also enhanced following acute SD. In contrast, repeated SD significantly elevated GR-ir at the hypothalamic paraventricular nucleus and CA1 and CA3 layers of the hippocampus compared to all other groups. Our study supports that a brief 4h sleep deprivation period is sufficient to induce delayed neurochemical changes.

Effects of gestational stress: 2. Evaluation of male and female adult offspring.

Physical restraint applied during gestation is a commonly employed animal model of human pregnancy stress. The consequences of such a paradigm have been extensively investigated in adult male rats using a variety of physiological and behavioral measures. The behavioral repertoire of female offspring, however, has been largely ignored. The current study examines adult offspring-male and female Long Evans rats (55-90 days of age) and is a follow-up report to the consequences of maternal restraint (gestation days 10 through 19) in mother rats and their juvenile offspring. Physiological measures included weight and estrous cycle regularity. Elevated plus maze and emergence tests were used to measure anxiety, and the T-maze test, cognition. Data were analyzed via hierarchical linear modeling to account for the nesting of offspring within litters. Compared to same-sex controls, males from stressed mothers displayed a progressive attenuated weight gain over experimental weeks while females from stressed mothers maintained a stable, lower weight throughout. Twenty-five percent of females in the stressed group and none in the control group displayed irregular cycles in the first week of testing; on subsequent weeks, this group discrepancy ranged from 1% to 11%. Subtle effects were observed in anxiety measures: an interaction between sex and stress group in the analysis of head dip behavior in the elevated plus maze and decreased emergence latencies in stress groups. Results demonstrate the importance of examining the effects of maternal stress in offspring of both sexes at various developmental stages.

Effects of gestational stress: 1. Evaluation of maternal and juvenile offspring behavior.

In both humans and animals, stress experienced during gestation is associated with physiological changes and disruptions in emotional function and cognitive ability in offspring; however, much less is known about the effects of such stress in mothers. In animal models, physical restraint is commonly employed to induce stress during gestation and results in elevated postpartum maternal anxiety and changes in maternal care. The purpose of the current study was to evaluate the consequences of restraint stress applied on gestation days 10 through 19 in mother rats and their juvenile offspring. Progeny were reared by birth mothers. Preterm anxiety was assessed in the elevated plus maze and maternal behavior in the retrieval test. Cognitive (T-maze) and anxiety measures (elevated plus maze and emergence) were applied to a subset of male and female offspring at 30-31 days of age. Weight and litter characteristics were also recorded. Mother rats exposed to stress during gestation had attenuated weight gain, elevated anxiety-like behavior, and reduced maternal care. Stressed mothers also had fewer pups and an elevated offspring mortality rate. The consequences of gestational stress in offspring were subtle and gender-dependent. Only juvenile females displayed marginal effects of gestational stress in the form of elevated anxiety-like behavior and attenuated weight gain. In the current study, although gestational stress had robust effects in the mother rat, these did not translate to similar changes in offspring behavior. The importance of focusing research on maternal responses to gestational stress is highlighted by these findings.