Maternal Deprivation Increases Anxiety- and Depressive-Like Behaviors in an Age-Dependent Fashion and Reduces Neuropeptide Y Expression in the Amygdala and Hippocampus of Male and Female Young Adult Rats.

Maternal deprivation for 24 h produces an immediate increase in basal and stress-induced corticosterone (CORT) secretion. Given the impact of elevated CORT levels on brain development, the goal of the present study was to characterize the effects of maternal deprivation at postnatal days 3 (DEP3) or 11 (DEP11) on emotional behavior and neuropeptide Y immunoreactivity (NPY-ir) in the basolateral amygdala (BLA) and dorsal hippocampus (dHPC) of male and female rats. Litters were distributed in control non-deprived (CTL), DEP3, or DEP11 groups. In Experiment 1, within each litter, one male and one female were submitted to one of the following tests: novelty suppressed feeding (NSF), sucrose negative contrast test (SNCT), and forced swimming test (FST), between postnatal days 52 and 60. In Experiment 2, two males and two females per litter were exposed to the elevated plus maze and 1 h later, perfused for investigation of NPY-ir, on PND 52. The results showed that DEP3 rats displayed greater anxiety-like behavior in the NSF and EPM, compared to CTL and DEP11 counterparts. In the SNCT, DEP3 and DEP11 males showed less suppression of the lower sucrose concentration intake, whereas all females suppressed less than males. Both manipulated groups displayed more immobility in the FST, although this effect was greater in DEP3 than in DEP11 rats. NPY-ir was reduced in DEP3 and DEP11 males and females in the BLA, whereas in the dHPC, DEP3 males showed less NPY-ir than DEP11, which, in turn, presented less NPY-ir than CTL rats. Females showed less NPY-ir than males in both structures. Because the deprivation effects were more intense in DEP3 than in DEP11, in Experiment 3, the frequency of nursing posture, licking-grooming, and interaction with pups was assessed upon litter reunion with mothers. Mothers of DEP11 litters engaged more in anogenital licking than mothers of DEP3 litters. The present results indicate that maternal deprivation changed affective behavior with greater impact in the earlier age and reduced the expression of NPY in emotion-related brain areas. The age-dependent differential effects of deprivation on maternal behavior could, at least in part, explain the outcomes in young adult rats.

Association of 24 h maternal deprivation with a saline injection in the neonatal period alters adult stress response and brain monoamines in a sex-dependent fashion.

Maternal deprivation (MD) disinhibits the adrenal glands, rendering them responsive to various stressors, including saline injection, and this increased corticosterone (CORT) response can last for as long as 2 h. In the present study, we tested the hypothesis that association of MD on day 11 with a saline injection would alter emotional behavior, CORT response, and brain monoamine levels, in male and female adult rats. Rats were submitted to the novelty suppressed feeding (NSF), the sucrose negative contrast test (SNCT), social investigation test (SIT), and the elevated plus maze (EPM). One quarter of each group was not tested (providing basal values of CORT and brain monoamines) and the remainder was decapitated 15, 45, or 75 min after the EPM, to assess CORT reactivity. Monoamine levels were determined in the hypothalamus (HPT), frontal cortex (FC), amygdala (AMY), ventral, and dorsal hippocampus (vHPC, dHPC, respectively). MD reduced food intake, in the home-cage, and latency to eat in the NSF in both sexes; females explored less the target animal in the SIT and explored more the open arms of the EPM than males; the CORT response to the EPM was greater in maternally-deprived males and females than in their control counterparts, and this response was further elevated in maternally-deprived females injected with saline. Regarding monoamine levels, females were less affected, showing isolated effects of the stressors, while in males, MD increased 5-HT levels in the HPT and decreased this monoamine in the FC, MD associated with saline reduced dopamine levels in all brain regions, except the HPT. MD at 11 days did not alter emotional behaviors in adult rats, but had an impact in neurobiological parameters associated with this class of behaviors. The impact of MD associated with saline on dopamine levels suggests that males may be vulnerable to motivation-related disorders.

Unpredictable chronic prenatal stress and manifestation of generalized anxiety and panic in rat's offspring.

Often the manifestation of anxiety cannot be explained by known environmental or hereditary factors. With this perspective, it has been reported that prenatal stress may lead to emotional disturbances in the offspring. However, studies relating prenatal stress to anxiety are controversial and generally the stressors used do not mimicks the reality experienced by mothers. Thus, this investigation evaluated the effects of an unpredictable chronic stress scheme applied in one of the three gestational weeks of rats on the manifestation of generalized anxiety and panic disorder in the progeny (males), analyzing, respectively, the avoidances and escapes in the elevated T-maze, at the 1st, 3rd or 6th month of progeny life. Control offspring showed increased generalized anxiety disorder and reduced panic at 6 months. The effects of prenatal stress depended on the gestational week where it occurred and on the progeny age: during the 1st gestational week the generalized anxiety decreased in 6 month old rats. Animals in the 3rd month, prenatally stressed during the last gestational week, showed anxiogenesis and panicogenesis, but effects reverted at the 6th month, when they presented anxiolysis and no changes related to panic. Together the results show that not only the gestational period in which the aversive experience occurred was important, but the age of the evaluated progeny, since the type and the intensity of behaviors related to anxiety may vary with the developmental stage. For the model of stress used in the present study, the effects of prenatal stress were more prominent when the exposure occurred during the 3rd gestational week in rats.

Impact of social separation during pregnancy on the manifestation of defensive behaviors related to generalized anxiety and panic throughout offspring development.

The multiple insecurities, anatomical, physiological and psychological changes arising from the gestational period can generate an overload of stress in the mother and cause disturbances in the offspring, affecting it throughout its development. The existing analysis linking prenatal stress and offspring's anxiety have divergent results, being limited as to gestational week, type of stressor and age of progeny's assessment. Social separation has been described as a stressor that causes increase in anxiety. Thus, the present study evaluated the effects of social separation applied in one of the three gestational weeks of rat dams on the manifestation of the defensive behaviors related to generalized anxiety disorder and panic in the Elevated T Maze of the male progeny in three stages of development (1, 3 or 6 months of life). It was found, in the offspring of grouped (control) dams, increased behaviors associated with generalized anxiety disorder and a reduction of panic-like behaviors throughout development. For animals whose dams were socially separated during pregnancy, the most critical period of exposure was the 2nd gestational week, which affected the acquisition of aversive memory, demonstrated by the impairment on learning of avoidances of the offspring in all ages evaluated. Stressor exposure in this week also increased the avoidances, related to generalized anxiety of progeny in the 1st month and decreased escapes, related to panic in the 3rd month of life and, at the age of 6 months old, an inverse situation, with the reduction of the defensive behaviors associated to generalized anxiety disorder. The results show that, when assessing effects of prenatal stress on the manifestation of anxiety, not only the period of exposure is important, but also the age of offspring assessed.