Blockade of Opiodergic System During Early Weaning Reverts Feeding Behavior Altered Patterns.

Adverse experiences that occur during the early stages of life can have permanent repercussions in adulthood. Among these experiences, early weaning is one that can alter the molecular, cellular, and behavior patterns in later life. Centered on this fact, the objective of the current study was to evaluate the effect of early weaning at 15 days of life of Wistar rats on their feeding behavior and if the opioidergic system blockade would cause a reversal of these outcomes. Experimental groups were formed based on the weaning period of each litter. On postnatal day 15, the group D15 was weaned and, on postnatal day 30 (natural weaning), the group D30 was weaned. The rats weaned on postnatal day 15, and administered subcutaneous Naltrexone (3 mg/kg) were from group D15 + NTX. Those weaned at 15 days of age exhibited higher depressive-like behavior, lesser reactivity time to sucrose, and higher intake of palatable food than the control group. The Naltrexone administration was observed to reverse some outcomes, such as increasing the reactivity time to sucrose and decreasing the quantity of palatable food consumed, to levels similar to those of the control group. Together, the findings of the present study are indicative of the vital role played by the opioidergic system in inducing the changes noted in the eating behavior patterns during adulthood, post early weaning.

Early life stress induced by maternal separation during lactation alters the eating behavior and serotonin system in middle-aged rat female offspring.

Stressful events occurring during early life have been related to behavioral and neurochemical disturbances. Maternal separation during the first two weeks of life is a traumatic event that strongly affects the feeding behavior and serotonergic system of the progeny in adulthood. As this system modulates the feeding behavior, the present study aimed at investigating the effects of maternal separation-induced stress on both the feeding behavior and serotonergic system of the middle-aged female rats by manipulating this system using fluoxetine, a selective serotonin transporter inhibitor. Lactating Wistar rats were separated from their litters from postnatal day 2 (PND 2) to PND 14 for 3 h in the dark phase of the circadian cycle. The maternally separated (MS) and control (C) groups were distinguished from each other based on the incidence or absence of maternal separation (early life stress). All the analyses were done on the female offspring from one-year of age. Maternal separation anticipated the satiety point in these females. This anticipation was linked to lower food intake, meal duration and meal size. These results mirrored the effects of fluoxetine in the control animals. Furthermore, maternal separation was associated with 5ht1b serotonin receptor hyperexpression in the hypothalamus. These findings demonstrate that maternal separation has long-lasting effects on the eating behavior and serotonergic system and that this system could be responsible for mediating these behavioral outcomes.

Early weaning modulates eating behavior and promotes hypofunction of the serotonergic (5HT) system in juvenile male rats.

Early life stress (ELS) has been associated with developmental impairments. Early weaning (EW) is a postnatal stress model consisting of interruption of lactation and maternal care. The 5HT-system has been associated with neurobehavioral modulations promoted by ELS. Thus, the present work aims to investigate the effects of early weaning on feeding behavior and serotonergic system of juvenile male rats. For this, rats were submitted to early (PND15) or natural (PND30) weaning and had the body weight, food intake in circadian phases, and food intake in response to fenfluramine assessed. mRNA expression of serotoninergic receptors (5HT1A and 5HT2C) and transporter (SERT) was assessed in the hypothalamus and brainstem, as well as NPY and POMC mRNA expression in hypothalamus. The results show that early weaning promoted changes in the percentage of weight gain during lactation period and increase in body weight at PND40. It was also observed that EW promoted increase and decrease in food intake in light and dark phase, respectively, and leads to a decreased action of fenfluramine on inhibition of food intake. In addition, early weaning promoted increased NPY and SERT mRNA expression in the hypothalamus and 5HT2C in the brainstem. Together, the data indicate that the stress caused by early weaning impairs the eating behavior of juvenile male rats through hypofunction of the 5HT-system.

Early weaning leads to disruption of homeostatic and hedonic eating behaviors and modulates serotonin (5HT) and dopamine (DA) systems in male adult rats.

Early weaning is associated with disruption of eating behavior. However, little is known about the mechanisms behind it. 5HT and DA systems are key regulators of homeostatic and hedonic eating behaviors, respectively. Thus, this study aims to evaluate the effects of early weaning on feeding behavior and 5HT and DA systems. For this, rats were submitted to regular (PND30) or early weaning (PND15) and between PND250 and PND300 were evaluated food intake of standard diet in response to 4 h food deprivation, during the 24 h period and per phase of the circadian cycle, in addition to the palatable food intake. Additionally, body mass and mRNA expression of 5HT1B, 5HT2C, SERT, DRD1 and DRD2 were evaluated in the hypothalamus and brainstem. The results demonstrate that early weaning promoted an increase in standard food intake in response to a 4 h food deprivation in the 24 h period and in the dark phase of the circadian cycle, in addition to an increased palatable food intake. No differences in body mass between regular or early weaning were observed. In the hypothalamus, increased mRNA expression of SERT and DRD1 was observed, but decreased 5HT1B mRNA expression. In the brainstem, the expression of 5HT1B, SERT, 5HT2C, DRD1 and DRD2 was increased in early weaned rats. In a nutshell, the stress promoted by early weaning has programmed the animals to be hyperphagic and to increase their palatable food intake, which was associated with modulation of 5HT and DA systems.

Dual exposure to stress in different stages of development affects eating behavior of male Wistar rats.

Maternal separation stress is a model of early life stress performed by the separation between dam and pups in the first days of life. The consequences of this early stress have been demonstrated on various behaviors, including feeding behavior. The results, however, are still controversial and it seems that a second exposure to stress later in life exacerbates the adverse outcomes. The present study aimed to determine the effects of maternal separation as a model of stress in early life, with or without a later life stress experience on eating behavior. Lactating Wistar rats were separated from their litters from postnatal day 2 (PND 2) to PND 14 for 3 h in the dark phase of the circadian cycle. The groups control (C) and separated (S) were composed. The assessment of food intake was performed between the ages of 60 and 150 days of life with a group that experienced only the early stress by maternal separation and with a second group that experienced the pre-weaning maternal separation stress and the food stress from 60 days of age. This food stress consisted of allowing visual and olfactory exposure of the animals to palatable food but did not allow the feeding. Maternal separation promoted higher palatable food and lower standard diet intake only after a double exposure to stress. Besides, the double exposure to stress promoted weight loss and an anxiety-like behavior. These outcomes were associated with a resistance to the anorectic effects of fluoxetine suggesting an alteration of the serotonergic system. Together, these findings indicate that maternal separation stress has long-lasting consequences on eating behavior, and that the dual exposure to stress seems more harmful to eating behavior outcomes. In addition, the results suggest that the serotonergic system is one candidate as the system mediating these alterations.

Undernutrition during pregnancy and lactation increases the number of fos-cells in the reward system in response to a 5-HT6 receptor agonist in male adolescent rats.

Undernutrition promotes morphofunctional adaptations in neuroanatomical circuits, leading to behavioural changes. Adolescence is a period of vulnerability for these adaptations, such as the control of food intake and the serotonergic system. The serotonergic system is capable of promoting satiety. However, its role in hedonic control has not been fully elucidated. The involvement of the 5-HT6 receptor in motivational feeding behaviours was recently observed. Therefore, we aimed to evaluate the effect of a 5-HT6 receptor agonist on food intake and neuronal activation in areas of the reward system in adolescent rats subjected to perinatal protein undernutrition. Wistar rats were divided into two groups according to nutritional manipulation during gestation and lactation. It has been observed that undernourished animals present greater neuronal activation in response to the 5HT-6 receptor agonist in areas of the food reward system.

Pre-weaning maternal separation increases eating later in life in male and female offspring, but increases brainstem dopamine receptor 1a and 2a only in males.

Maternal separation stress (MS) is a model of early life stress performed by the separation between dam and pups in the first days of life. This model has been associated with eating behavior and dopaminergic system abnormal phenotypes. This study aims to investigate whether maternal separation in the light or dark phase of the circadian cycle promotes phenotypic adjustments in the eating behavior and the dopamine system in both males and females. Lactating Wistar rats were separated from their litters from postnatal day 1 (PND 1) to PND 14 for 6 h in the light or dark phase of the circadian cycle. The groups of female control (FC), male control (MC), female rat separated in the dark (FSD), male rat separated in the dark (MSD), female rat separated in the light (FSL), and male rat separated in the light (MSL) were composed. The assessment of food intake was performed at the age of 120-150 days and the analysis of brainstem drd1a and drd2a dopamine receptors expression at 180 days of life. Maternal separation promoted higher palatable diet intake independent on sex and circadian cycle. On the other hand, drd1a and drd2a dopamine receptors expression were higher only in males separated in the dark phase of the circadian cycle. These findings demonstrate that maternal separation effects on feeding behavior do not depend on sex and circadian cycle, but the effects on dopamine receptors expression depend on sex and circadian cycle.

Low protein diet during gestation and lactation increases food reward seeking but does not modify sucrose taste reactivity in adult female rats.

INTRODUCTION: Nutritional deficiencies during neural development may lead to irreversible changes, even after nutritional rehabilitation, promoting morphological and functional adaptations of structures involved with various behaviours including feeding behaviour. However, the ability of the exposure low protein diet during gestation and lactation to affect the hedonic component of food intake is still poorly understood, especially in females. METHODS: Wistar rats were divided into two groups according to the diet offered to the dams during pregnancy and lactation: control female (CF; diet with 17% protein, n=7) and low protein female (LPF; diet with 8% protein, n=7). The following parameters were evaluated: (a) body weight during weaning, 30, 45, 60, 75, 90 days of life; (b) standard diet intake from 110 to 132 days of life; (c) fat diet and consumption of simple carbohydrates (HFHS) for 1h at 145 days of life; (d) incentive runway task 60 days after 82 days of life; (e) taste reactivity at 90 days of life; and (f) neuronal activation in the caudate putamen, amygdala, paraventricular nucleus of the hypothalamus under stimulus HFHS at 145 days of life. RESULTS: The exposure, a low protein diet during gestation and lactation, decreased the body weight throughout the study period from weaning to 90 days of life. However, there was no significant change in the body weight of low protein females from 110 to 132 days of life compared with the control females. There was an increase in the rate of the search for reward and reduced the latency of the perception of bitter taste. The exposure, a low protein diet during gestation and lactation, also promoted hypophagy in adult females compared with control animals. The low protein female had increased HFHS diet consumption compared with the control. Undernutrition increased neuronal activation in response to HFHS diet consumption compared with female controls in the amygdala and in the caudate putamen. CONCLUSION: Females subjected to the exposure, a low protein diet during gestation and lactation, exhibit hypophagy on a standard diet but a higher consumption of a diet rich in lipids and simple carbohydrates. And also were more motivated by the pursuit of reward and reduced latency of the bitter taste reactivity, and increased the number of immunoreactive cells c-fos protein activated in the caudate putamen, amygdala and paraventricular nucleus.

Early exposure of dams to a westernized diet has long-term consequences on food intake and physiometabolic homeostasis of the rat offspring.

This study evaluated the long-term effects of a westernized diet during pregnancy and lactation. Female Wistar rats (n = 12) were divided into two groups according to their food intake, namely, control (C) or westernized (W) diet, throughout pregnancy/lactation. On the 21st day, the male pups were weaned on a standard diet as follows: Control diet (CC) (n = 8) and westernized diet in perinatal life followed by control diet post weaning (WC) (n = 8). The levels of fasting (12 h) serum glucose, triglycerides (TG), and total cholesterol and fraction in the pups were determined. During weaning, the WC group showed 14% greater body weight (p < 0.001). In the adulthood, the offspring from dams fed on westernized diet showed hyperphagia, hyperinsulinism, hypertriglyceridemia, higher fat visceral weight, higher very-low-density-lipoprotein cholesterol level, decreased high-density-lipoprotein cholesterol level, and altered glucose tolerance test. In conclusion, maternal western-style diet in early life altered long-term food intake, visceral fat pad, insulin, glucose and lipid serum, and increased risk of metabolic disorders.