Dysfunctional nurturing behavior in rat dams with limited access to nesting material: a clinically relevant model for early-life stress - PubMed (original) (raw)

Dysfunctional nurturing behavior in rat dams with limited access to nesting material: a clinically relevant model for early-life stress

A S Ivy et al. Neuroscience. 2008.

Abstract

Background: Early-life emotional stress may be associated with affective and cognitive disorders later in life, yet satisfactory animal models for studying the underlying mechanisms are limited. Because maternal presence and behavior critically influence molecular and behavioral stress responses in offspring, we sought to create a model of dysfunctional, fragmented maternal nurturing behavior that would, in turn, provoke chronic early-life stress in the offspring.

Methods: Sprague-Dawley rat dams' nursing and nurturing behaviors were altered by limiting their ability to create satisfactory nests during postpartum days 2-9. Maternal behavior was observed throughout the diurnal cycle, and the frequency and duration of nurturing behaviors were scored. In addition, potential stress and anxiety of the dams were assessed using behavioral, molecular and hormonal measures.

Results: Both the quantity and the quality of dams' care of their pups were profoundly influenced by restriction of nesting materials in their cages: licking/grooming activities decreased and the frequency of leaving the pups increased, resulting in fragmented interactions between the dams and pups. The abnormal activity patterns of the dams were accompanied by increased anxiety-like behavior in the open field, but not in the elevated plus maze tests. Additionally, dams' plasma corticosterone levels and adrenal weights were augmented, suggesting chronic stress of these dams. By the end of the limited-nesting, stress-inducing period, hypothalamic corticotropin releasing hormone (CRH) mRNA expression was reduced in the limited-nesting dams, while arginine-vasopressin (AVP) mRNA levels were not significantly affected.

Conclusion: Limiting dams' ability to construct a nest for their pups leads to an abnormal repertoire of nurturing behaviors, possibly as a result of chronic stress and mild anxiety of the dams. Because the fragmented and aberrant maternal behavior provoked chronic stress in the pups, the limited-nesting paradigm provides a useful tool for studying the mechanisms and consequences of such early-life stress experience in the offspring.

PubMed Disclaimer

Figures

Fig. 1

Abnormal patterns of maternal nurturing behaviors of dams in cages with restricted nesting material (early-stress or ES). (A) Duration of ES dams’ licking and grooming (L&G) the pups was markedly decreased during dark-phase observation periods on postpartum days 2–5 (n = 7 dams per group, two-way ANOVA, effects of cage environment, F = 4.67, p < 0.05; + indicates the results of student’s _t_-test comparison of control and ES duration on P2). _(B)_ During the light phase, there were no significant differences in L&G duration (two-way ANOVA, F = 1.686, p > 0.05). (C) Pups in restricted nesting cages were significantly more likely to be displaced from the nest (p < 0.05; student’s _t_-test). *denotes significant difference from the controls (p < 0.05).

Fig. 2

Maternal nurturing behaviors of dams maintained in cages with restricted nesting material (ES) were inconsistent and fragmented. (A,B) Mean number of epochs during which ES dams were found away from the pups was significantly higher during postpartum days 2–5, during both the light-phase (A; two-way ANOVA, effect of cage environment, F = 47.19, p < 0.001; effect of postnatal day, F = 14.98, p = 0.001) and the dark-phase (B; two-way ANOVA, effect of cage environment, F = 5.16, p < 0.05) observation periods (n = 7 per group). (C,D) Representative examples of maternal caring activities from one control and one ES dam, during the light-phase (C) and dark-phase (D) observations, performed on postpartum day 5. Each individual color depicts the predominant behavior during the epoch / square. Blue: nursing; red: away from pups (off pups or out of the nest); yellow: licking and grooming pups; pink: dam eating and drinking, away from pups; green: dam licking and grooming self, away from pups. This graphic representation illustrates the fact that in control dams, each behavior typically lasted for several consecutive 3 minute epochs, whereas ES dams tended to switch behaviors frequently and unpredictably. (E) The behavior of ES dams (n = 7 per group) was less consistent, with frequent switching from one type of activity to another, during the dark, high activity portion of the diurnal cycle. This erratic behavior is reflected by a higher behavior score, which denotes increased numbers of initiating a new behavior during consecutive observation epochs (see the Results for detailed description of this score). (F) Mean duration of arched-back nursing episodes was influenced by the ES cage environment throughout the light-phase of the first 4 days in this environment (two-way ANOVA, effect of cage environment, F = 5.67, p < 0.05). *p < 0.05; students _t_-test.

Fig. 3

Dams rearing pups in restricted nesting material (ES) cages demonstrated increased anxiety in some but not other tests (n = 5 dams per group). In the open field task (A), percent time ES dams spent in the center of an open field chamber was significantly decreased (p < 0.05, _t_-test), without apparent alterations in freezing, licking and grooming behaviors (B). (C,D) Activities in the elevated plus maze were similar among control and ES dams; there were no differences in time spent on open vs. closed arms, nor in the number of arm entries., *p < 0.05; students _t_-test.

Fig. 4

Physiological and molecular parameters of chronic stress were apparent in dams that reared their offspring in restricted nesting material (ES) cages. (A) Mean adrenal gland weight per body weight was higher than in controls (p < 0.05), and body weight was not significantly altered (see text). (B) Basal AM plasma corticosterone levels were significantly elevated in ES dams compared with controls (n = 4 dams / group; p < 0.05). (C,D) Corticotropin-releasing hormone (CRH) expression in the hypothalamic paraventricular nucleus PVN was reduced on postpartum day 9, following a week of the ES cage environment (p < 0.05). (E,F) However, there were no apparent changes in the expression of arginine-vasopressin (AVP). *p < 0.05; students _t_-test.

References

1. Avishai-Eliner S, Hatalski CG, Tabachnik E, Eghbal-Ahmadi M, Baram TZ. Differential regulation of glucocorticoid receptor messenger RNA (GR-mRNA) by maternal deprivation in immature rat hypothalamus and limbic regions. Dev Brain Res. 1999;114:265–268. - PMC - PubMed
1. Avishai-Eliner S, Eghbal-Ahmadi M, Tabachnik E, Brunson KL, Baram TZ. Down-regulation of hypothalamic corticotropin-releasing hormone messenger ribonucleic acid (mRNA) precedes early-life experience-induced changes in hippocampal glucocorticoid receptor mRNA. Endocrinol. 2001a;142:89–97. - PMC - PubMed
1. Avishai-Eliner S, Gilles EE, Eghbal-Ahmadi M, Bar-El Y, Baram TZ. Altered regulation of gene and protein expression of hypothalamic-pituitary-adrenal axis components in an immature rat model of chronic stress. J Neuroendocrinol. 2001b;13:799–807. - PMC - PubMed
1. Avishai-Eliner S, Brunson KL, Sandman CA, Baram TZ. Stressed-out, or in (utero)? Trends Neurosci. 2002;6:319–329. - PMC - PubMed
1. Bhatnagar S, Dallman MF. Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress. Neurosci. 1998;84:1025–1039. - PubMed

Dysfunctional nurturing behavior in rat dams with limited access to nesting material: a clinically relevant model for early-life stress - PubMed (original) (raw)