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.

Astrocytic expression of GFAP and serum levels of IL-1ß and TNF-α in rats treated with different pain relievers

ABSTRACT Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP) and the serum levels of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days- (1) amitriptyline (Amt-10 mg/kg/day, by gavage); (2) gabapentin (Gb-60 mg/kg/day, by gavage; (3) methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]); (4) morphine (Mo-10 mg/kg/day, IP); or (5) 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc). The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1ß and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1ß decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo