Maternal separation stress reduced prenatal-ethanol-induced increase in exploratory behaviour and extracellular signal-regulated kinase activity.

Autor: Swart PC; University of Cape Town, Faculty of Health Sciences, Department of Human Biology, Observatory, 7925 South Africa. Electronic address: swrpat003@myuct.ac.za., Russell VA; University of Cape Town, Faculty of Health Sciences, Department of Human Biology, Observatory, 7925 South Africa. Electronic address: vivienne.russell@uct.ac.za., Dimatelis JJ; University of Cape Town, Faculty of Health Sciences, Department of Human Biology, Observatory, 7925 South Africa. Electronic address: frxjac007@myuct.ac.za.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2019 Jan 01; Vol. 356, pp. 470-482. Date of Electronic Publication: 2018 Jun 13.
DOI: 10.1016/j.bbr.2018.06.004
Abstrakt: In an attempt to better represent the aetiology of fetal alcohol spectrum disorder (FASD) and the associated psychological deficits, prenatal-ethanol exposure was followed by maternal separation in a rat model in order to account for the effects of early-life adversities in addition to in utero alcohol exposure. Extracellular signal-regulated kinase 1/2 (ERK1/2) and glycogen synthase kinase 3-β (GSK3β) are converging points for many signalling cascades and have been implicated in models of FASD and models of early-life stress. Therefore, these kinases may also contribute to the behavioural changes observed after the combination of both developmental insults. In this study, ethanol-dams voluntarily consumed a 0.066% saccharin-sweetened 10% ethanol (EtOH) solution for 10 days prior to pregnancy and throughout gestation while control-dams had ad libitumaccess to a 0.066% saccharin (sacc) solution. Whole litters were randomly assigned to undergo maternal separation (MS) for 3 h/day from P2 to P14 while the remaining litters were left undisturbed (nMS). This resulted in 4 experimental groups: control (sacc + nMS), MS (sacc + MS), EtOH (EtOH + nMS) and EtOH + MS. Throughout development, EtOH-rats weighed less than control rats. However, subsequent maternal separation stress caused EtOH + MS-rats to weigh more than EtOH-rats. In adulthood both MS- and EtOH-rats were hyperactive but the combination produced activity levels similar to that of control rats. All treated animals (MS-, EtOH- and EtOH + MS-rats) demonstrated a negative affective state shown by increased number and duration of 22 kHz ultrasonic vocalizations compared to control rats. Prenatal-ethanol exposure increased the P-GSK3β/GSK3β ratio in the prefrontal cortex (PFC) and maternal separation decreased the P-GSK3β/GSK3β ratio in the dorsal hippocampus (DH) of adult rats. However, maternal separation stress decreased the effect of prenatal-ethanol exposure on the P-ERK/ERK ratio in the PFC and DH and reduced prenatal-ethanol-induced hyperactivity. Therefore, indicating a significant interaction between prenatal-ethanol exposure and early-life stress on behaviour and the brain and may implicate P-ERK1/2 signalling in exploratory behaviour.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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