Maternal Separation in Rats Leads to Anxiety-Like Behavior and a Blunted ACTH Response and Altered Neurotransmitter Levels in Response to a Subsequent Stressor

Abstract

Adverse early life experiences can have a negative impact on behavior later in life. We subjected rat pups to maternal separation and determined the effect's thereof on adult behavior. We removed rat pups from their mothers for 3 h daily from postnatal days 2 to 14. While controls were reared normally on day 60, the behaviors of the rats were tested using the elevated plus-maze. Some rats were subsequently subjected to restraint stress for a 10-min period. Trunk blood was collected for basal, as well as 15- and 60-min postrestraint stress ACTH determinations. Neurotransmitter levels (noradrenaline (NA), serotonin (5HT), and their metabolites, MHPG and 5HIAA, respectively) were also determined at basal, immediately and 15-min post-restraint stress in the hypothalamus, hippocampus, and frontal cortex in another group of animals. The amount of entries into the arms of the elevated plus-maze was significantly reduced in the separated animals, indicating decreased locomotion. They spent significantly more time in the closed arms of the maze. A significant increase in defecation frequency was noted. These observations suggested anxious behavior. Basal ACTH levels were significantly higher in separated animals. At 15-min post-restraint stress, the ACTH levels were significantly lower than controls, indicating a blunted stress response. A decrease in noradrenaline was noted first in limbic regions and an increase in 5HIAA levels was found in the frontal cortex and hippocampus. We conclude that maternal separation induced abnormal behaviors and stress responses that were associated with altered neurotransmitter levels.

Early-Life Immune Challenge: Defining a Critical Window for Effects on Adult Responses to Immune Challenge

“…Further evidence for this is that maternal behavior has been shown to be critical for adult emotionality in rats. For instance, separation from the mother has been shown to alter responses in behavioral tests of anxiety including the elevated plus maze (Daniels et al, 2004;Kalinichev et al, 2002). As we saw no significant differences in the anxiety responses elicited by the elevated plus maze in the present study, it is unlikely that there were marked differences in maternal behavior directed towards LPS-or saline-injected pups.…”

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

“…Wei et al [41] also found that mice exposed to brief daily separation for 3 hours, a model of early life stress, showed higher DNA methylation at the ribosomal DNA (rDNA) promoter, lower RNA levels and blunted hippocampal growth during the second week of life. The same model of 3-hour daily separation during the first 21 days of life has been previously associated with anxiety increase in adult rats [42]. And, among the genes whose expression was altered in a model of prenatal stress in mice, both in the frontal cortex and hippocampus, it was DNMT1, that was accompanied by an enrichment in 5-methylcytosine and 5-hydroxymethylcytosine at BDNF gene regulatory regions and a decrease in BDNF expression [43].…”

The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning

“…By contrast, longer periods of separation caused long lasting, anxiogenic, i.e. detrimental effects in the offspring (Huot et al 2001;Kalinichev et al 2002;Daniels et al 2004). …”