Elsevier

Pharmacological Reports

Volume 65, Issue 6, November–December 2013, Pages 1451-1461
Pharmacological Reports

Review
Early maternal separation: a rodent model of depression and a prevailing human condition

https://doi.org/10.1016/S1734-1140(13)71505-6Get rights and content

Abstract

The early life of most mammals is spent in close contact with the mother, and for the neonate, early maternal separation is a traumatic event that, depending on various conditions, may shape its behavioral and neurochemical phenotype in adulthood. Studies on rodents demonstrated that a very brief separation followed by increased maternal care may positively affect the development of the offspring but that prolonged separation causes significant amounts of stress. The consequences of this stress (particularly the hyperreactivity of the HPA (hypothalamic–pituitary–adrenal) axis are expressed in adulthood and persist for life. Maternal separation in rodents, particularly rats, was used as a model for various psychotic conditions, especially depression. The most popular separation procedure of a 3-h daily separation from the second to the 12th postpartum day yields a depression model of high construct and predictive validity. The results of studies on maternal separation in rats and monkeys prompt a discussion of the consequences of traditional procedures in the maternity wards of developed countries where attention is focused on the hygiene of the neonates and not on their psychological needs. This alternate focus results in a drastic limitation of mother-infant contact and prolonged periods of separation. It is tempting to speculate that differences in the course and severity of various mental disorders, which are usually less prevalent in underdeveloped countries than in developed countries (as noted by Kraepelin), may be related to different modes of infant care. Only recently has so-called kangaroo mother care (establishing mother-infant skin-to-skin contact immediately after birth) become popular in developed countries. In addition to its instant benefits for the neonates, this procedure may also be beneficial for the mental health of the offspring in adulthood.

Section snippets

Methodological problems

Although maternal separation is the most robust and common model of the disruption of the mother-offspring relationship, the reports on its effects in rats are often varied [58, 71]. Separation from dams is always a stressful procedure for rat pups, which respond to it with increased motor activity and decreased cardiac and respiratory rates [36]. The tactile and olfactory stimulation that pups constantly receive from their mother reduces the innate high levels of behavioral arousal of neonates

Frequency of separation

This procedure usually involves a repetitive separation. In most studies, the pups are separated once or twice every day. Alternatively, a single separation for a longer period of time can be used.

Timing

The separation procedure usually starts from the second postpartum day (PD) to day 10 or 14 and extends to PD21 (weaning) in some experiments. The separation period overlaps the stress hyporesponsive period, extending between PD4 and PD14 [105]. This natural defense against stress in neonates may

Neonate stress and mother behavior during separation

The neonatal rat is dependent upon the mother for thermoregulation, nutrition, the stimulation of urination and protection for the first two weeks of life [104], particularly because its brain at birth is roughly equivalent to a human brain at gestational ages 23–24 weeks [94]. Tactile sensory input from the mother, particularly skin-to-skin contact, augments the pups’ hypothalamic oxytocin concentrations [51], which is required for the expression of filial huddling preference [50], an element

Early maternal separation as a model of depression

Avalid animal model of psychotic depression may serve as a potent tool for both understanding the mechanisms of pathological changes and preclinically testing a variety of antidepressant treatments. Following 30 years of studies on the effects of early handling and maternal separation in rats, it was proposed that mother-infant separation may be considered an evolutionary model for human depression [112], and it is generally agreed that the MS180 procedure appears to fulfill the criteria for a

Brief maternal separation and Kangaroo Mother Care in humans

A vast body of evidence documents the adverse effects of child separation, maltreatment and abuse. The neglect or maltreatment of children in early developmental stages increases the risk of psychological disturbances such as anxiety, depression and psychoses in adulthood [9, 33, 48, 83], which are often resistant to treatment [14, 84], The earlier the infant encounters the adverse experience, the more prone it is to express anxiety and depression in adulthood [47]. However, as mentioned for

Acknowledgment

Supported by grant No. POIG.01.01.02-12-004/09-00, financed by the European Regional Development Fund.

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