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

Abstract

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 Life Stress and the Onset of Obesity: Proof of MicroRNAs’ Involvement Through Modulation of Serotonin and Dopamine Systems’ Homeostasis

“…On the other hand, we have been able to associate the EW with changes in gene expression of several components of the 5HT system in male and female rats, such as SERT, 5HT1B, and 5HT2C in hypothalamus and brainstem. Based on the patterns of expression in the brainstem and response to fenfluramine, we suggested a hypofunction of the serotonergic system in the EW animals ( Tavares et al, 2019 , 2020a , b ). All these changes in the 5-HT system were accompanied by alterations on feeding behavior, which indicate that the 5HT system control of feeding behavior can be modulated by ELS, which can be directly linked to the onset of obesity.…”

“…Conversely, both clinical and pre-clinical studies demonstrate that ELS is able to alter SERT activity (Wankerl et al, 2014;Van Der Knaap et al, 2015;Tavares et al, 2019Tavares et al, , 2020a. Interestingly, differences in SERT activity are observed in obesity, both in humans and animals (Giannaccini et al, 2013;Borgers et al, 2014;Zha et al, 2017).…”