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

Abstract

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.

Neuropeptide Y in PTSD, MDD, and chronic stress: A systematic review and meta‐analysis

“…Moreover, a dose response relationship between intranasal NPY and anxiety has been reported at higher doses of NPY, without significant side effects in animals (Sabban & Serova, ). Animal studies suggest that lower NPY levels are associated with depressive, anxiety‐like, and PTSD symptoms (Cohen et al, ; Miragaia et al, ). And, some pro‐depressant agents cause a drop in NPY (Desai, Borkar, Nakhate, Subhedar, & Kokare, ), which in turn is increased by antidepressants (Kotagale, Paliwal, Aglawe, Umekar, & Taksande, ).…”

Sex Differences in the Neuropeptide Y System and Implications for Stress Related Disorders

“…Extensive literature indicates that there are sex differences in the NPY system in relation to stress within both the central nervous system and periphery [ 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. In order to better understand its role in different biological processes, it is imperative to investigate NPY’s actions in a sex-specific manner.…”

“…However, when animals exposed to early-life stress were examined in adolescence, females tended to exhibit lower NPY expression in specific brain regions. Specifically, these females showed fewer NPY-immunoreactive neurons than males in both the basolateral amygdala and the hippocampus after exposure to maternal separation stress [ 66 ]. Furthermore, adult female rats had lower NPY peptide levels in the dorsal hippocampus after maternal separation stress than males [ 67 ].…”

“…Furthermore, adult female rats had lower NPY peptide levels in the dorsal hippocampus after maternal separation stress than males [ 67 ]. Early-life stress caused a decrease in NPY-expressing neurons and peptide levels in both females and males as compared to unstressed controls [ 66 , 67 , 128 ]. Perhaps stress acutely hyperactivates the NPY system, but it is attenuated after time in females.…”

An ADAR1 inducer attenuated the effects of social isolation on depressive-like behavior and ADAR1 (p110) in BALB/c mice

“…Studies have shown that animals or human beings that are in a state of social isolation for a long time will exhibit depressive-like behavior (Evans IEM et al, 2017;Kosofsky BE et al, 1987;Ge L et al, 2017;Chow PI et al, 2017;Li X et al, 2013). It is known that depressive-like behavior is related to abnormal brain development, abnormal serotonin levels, and neuroinflammation (Miragai AS et al, 2018;Xin F et al, 2018;Han L et al, 2018). However, the mechanism of depressive-like behavior induced by social isolation stress has not yet been fully elucidated.…”