The effects of early‐life stress on dopamine system function in adolescent female rats

Abstract

During adolescence, many neural systems, including the dopamine system, undergo essential remodeling and maturation. It is well known that early-life stress (ELS) increases the risk for many psychopathologies during adolescence and adulthood. It is hypothesized that ELS interferes with the maturation of the dopamine system. There is a sex bias in the prevalence of stress-related mental disorders. Information regarding the effects of ELS on brain functioning in females is very limited. In the current study, maternal separation (MS) procedures were carried out to study the effects of ELS on dopamine system functioning in adolescent female rats. Our study showed that MS increased the density of tyrosine hydroxylase immunoreactive fibers in the prelimbic cortex (PLC) and nucleus accumbens (Acb). These changes were accompanied by a decrease in the level of D5 receptor mRNA and an increase in D2 receptor mRNA expression in the PLC of MS females. Conversely, D1 and D5 receptor mRNA levels were augmented in the caudate putamen (CPu), while the expression of the D3 dopamine receptor transcript was reduced in MS females. Additionally, in the Acb, MS elicited a decrease in D2 receptor mRNA expression. At the behavioral level, MS increased apomorphine-induced locomotion; however, it did not change locomotor responses to selective D1/D5 receptor agonist and attenuated D2/D3 receptor agonist-triggered locomotion. Moreover, MS decreased D1/D5 receptor agonist-induced grooming behavior. These results indicate that ELS disrupts dopamine receptor function in the PLC and basal ganglia during adolescence in females and may predispose them to psychopathologies during adolescence and adulthood.

Mechanisms of Shared Vulnerability to Post-traumatic Stress Disorder and Substance Use Disorders

“…In the mesolimbic circuit, particularly within the VTA-NAc projection, ELS causes long-term changes in dopaminergic activity. Both animal and human studies have reported an increase in stressinduced dopamine release during adulthood (Hall et al, 1999;Brake et al, 2004;Pruessner et al, 2004;Yorgason et al, 2013), and animal studies have shown long-lasting changes in dopamine receptors including decreased NAc D2R expression in prenatally stressed rats treated with nicotine (Said et al, 2015) as well as in rats subjected to maternal separation (Majcher-Maślanka et al, 2017). As previously mentioned, decreased density of the D2R in the NAc is thought to be an important contributor to drug craving (Volkow et al, 1993.…”

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

“…Our previous study showed that DRD1 and DRD2 gene expression were increased in the brainstem of adult rats, accompanied by higher palatable food intake after MS (de Souza et al, 2018). The MS also modulates the DA system in other brain areas, such as PLC, NAcc, and striatum, changing the density of immunoreactive fibers of TH, and the mRNA expression of DRD2, DRD1, and DRD5 (Majcher-Maślanka et al, 2017). On the other hand, EW increases DRD1 mRNA expression in the hypothalamus and brainstem and DRD2 in the brainstem of middle-aged male rats (Tavares et al, 2020b).…”

Why are maternally separated females inflexible? Brain activity pattern of COx and c-Fos

“…Numerous studies have investigated the effects of early-life stress, but only in the past decade have females been included in the research cohorts (Barbosa Neto et al, 2012;Dalaveri, Nakhaee, Esmaeilpour, Mahani, & Sheibani, 2017;Dimatelis, Vermeulen, Bugarith, Stein, & Russell, 2016;Loi et al, 2015;Lukkes, Meda, Thompson, Freund, & Andersen, 2017;Majcher-maslanka, Solarz, Krzysztof, & Chocyk, 2017;Sun, Tu, Shi, Xue, & Zhao, 2014;Xiong, Yang, Wang, Xu, & Mao, 2014). In a previous study in our laboratory, we demonstrated how MS affects male rats' spatial memory (Banqueri, Méndez, & Arias, 2017), In the present study, we want to further explore spatial memory, in this case with females, while also testing cognitive flexibility.…”