Elsevier

Physiology & Behavior

Volume 84, Issue 4, 31 March 2005, Pages 607-615
Physiology & Behavior

Abnormal patterns of maternal behavior in a genetic animal model of depression

https://doi.org/10.1016/j.physbeh.2005.02.006Get rights and content

Abstract

The Flinders Sensitive Line (FSL) model is considered a genetic animal model of depression. Among other characteristics, FSL rats express stress-induced anhedonia and an abnormal dopaminergic system. Our hypothesis was that FSL rats would show abnormal maternal behaviors, especially reduced motivation to reach and care for pups and reduced licking and non-nutritive contact, based on their anhedonic characteristics. Mother–infant interactions were assessed by time limited observations in FSL and Sprague–Dawley (SD) controls. In study 1, differences were found in consummatory behaviors: FSL dams compared to SD dams showed less licking and significant decrease in non-nutritive contact from the first to the third postpartum weeks. In addition, shorter duration of nursing postures was seen in FSL compared to SD dams in the first week postpartum, and this difference was significantly increased by the third week postpartum. In study 2, after exposure to acute swim stress, differences emerged in appetitive behaviors: latencies to reach and care for pups were longer in FSL dams compared to controls, suggesting a stress-induced motivational deficit in FSL dams. Possible explanations, especially regarding the FSL dams' reward system are discussed.

Introduction

Depression is believed to occur in genetically predisposed persons that are exposed to stressful situations/experiences [1], [2]. Therefore, the use of a genetic animal model of depression in studying this disorder is appropriate and particularly relevant. Flinders Sensitive Line (FSL) rats were selectively bred from Sprague–Dawley (SD) rats, and were found to have face, construct and predictive validity, and thus they have been proposed as a genetic animal model for some aspects of human depression [3], [4]. Although the FSL line was first established on the basis of high sensitivity to cholinergic agonists (especially in lowering body temperature in response to diisopropyl fluorophosphates (DPF))–a characteristic that was found also in depressed humans [5], [6]–they were later found to have other depressive-like physiological and behavioral characteristics that correspond to the human depressive state (for review see Refs. [3], [7]).

The FSL rat has been suggested as a model for genetic vulnerability to stress-induced depression, because some of the rat behaviors that are analogous to human depressive symptoms are more prominent in FSL rats upon exposure to stressors [3], [7]. For example, one of the well-documented characteristics of FSL rats is stress-induced anhedonia, meaning that anhedonia (assessed by reduced saccharin consumption) becomes significantly more apparent in FSL rats compared to controls after exposing them to acute foot shock or to chronic mild stress [3], [7], [8], [9]. Nevertheless, lately it has been suggested that FSL rats have anhedonic characteristics even under baseline conditions, because without exposure to stress they showed reduced levels of bar-pressing for cocaine (a potent reward) but not for water [10]. Accordingly, extracellular dopamine levels of FSL rats in the nucleus accumbens (NAc, a limbic site in which the release of dopamine is associated with motivation, reward and hedonic tendencies) are lower than that of SD rats [11], and this difference is increased 60 min after exposure to forced swim stress [12].

The anhedonic characteristics of FSL rats may affect maternal behavior because the maintenance of maternal care is known to be mediated by the reinforcing value of the pups to the dam [13], [14], [15], [16], [17], [18]. Abnormal maternal care, in turn, is associated with developmental, emotional and social deficits both in human infants [19], [20], [21], [22], [23], and in rat pups [24], [25], [26], [27], [28], [29]. Research has shown that depression in human mothers may be a source of abnormal maternal environment [30]. In the current research we investigated the FSL rats as a model in which depression and maternal behavior can be related, especially considering their deficit in the reward system.

One should note that most of the research on FSL rats was conducted with adult males. There are some studies where both males and females were investigated, and a few studies in which only FSL females were used as subjects. According to a recent study conducted in our laboratory, postpartum FSL dams express longer durations of immobility in a variation of the forced swim test compared to postpartum Sprague–Dawely (SD) dams [31]. Given that postpartum FSL dams meet this widely accepted index for depressive-like behavior in rats [32], [33], we proceeded to study whether patterns of maternal behavior might also be altered in this line.

Specifically, we examined differences between FSL and SD dams in a 30-min. interaction with their pups, measuring the latencies and durations of various maternal behaviors. Animals from both lines were tested either in the first or in the third postpartum week. The use of two postpartum periods enabled us to investigate the developmental patterns of maternal care from early to late postpartum. However, the interpretation of the third week interaction in terms of the dam's characteristics was more difficult, because of the developmental stage of the pups that enables them to enlarge their relative involvement in the interaction. Since some behaviors of the FSL rats, especially those that relate to anhedonia, are better revealed after exposure to stressors, we also conducted a follow-up study in which exposure to acute swim stress preceded a 30-min interaction. This follow-up study was conducted only in the first week postpartum.

We expected to find different profiles of mother–infant interaction between the FSL and the SD dams, and that these differences would be enlarged after exposure to stress. Considering the anhedonic characteristics of the FSL rats and the reward mechanisms underlying mother–infant interactions, latencies (i.e. motivational/appetitive aspects of maternal behavior, see discussion below) to reach and care for pups were expected to be longer in FSL dams. Durations of non-nutritive contact and active pup related behaviors were expected to be lower in FSL dyads compared to controls, since these behaviors are highly correlated with increased dopamine levels in the nucleus accumbens [34], [35], [36], [37], [38]. As for nursing postures, we could not formulate a specific hypothesis from the current design because of the great mutual effects of dams and pups in this behavior [39], [40]. Furthermore, considering the characteristics of the FSL model (anhedonia on one hand and low motor activity on the other hand), it was difficult to dissociate the rewarding aspects of the nursing postures (as a crucial part of maternal behavior), from the motorically passive aspects of this behavior, in terms of its correlation with dopaminergic activity (see Ref. [41]).

Section snippets

General methods

Nulliparous SD and FSL female rats were mated with males from the same line in their breeding colonies, in the Developmental Psychobiology lab at Bar-Ilan University, Ramat-Gan, Israel. Both lines are somewhat inbred because of the relatively small number of original parents. Pregnant rats were housed individually in a clean polypropylene cage (18.5 cm height × 26.5 cm width  × 43 cm length), with a stainless steel wire lid and wood shavings as bedding material. Food and water were freely

Discussion

The aim of the current research was to examine whether female FSL rats express different profiles of maternal behavior compared to female SD rats. We examined primiparous mother–infant interactions of same-line dyads. As an initial study, we were interested in the pattern of maternal behavior of FSL dams towards their own infants, in order to obtain at least a partial answer to the question of whether an abnormal maternal environment that infants of depressed mothers are exposed to can be

Footnotes and notes

FRL rats were bred from SD rats for hypo-sensitivity to a cholinergic agonist [3], [7]; both FRL and SD rats are legitimate control groups for FSL rats, because in most cases they are not significantly different from each other [3]. We, and others, used SD rats as controls, as they represent the background strain variability from which the FSL were derived. In contrast, FRL rats were selectively bred for an opposite characteristic.

A portion of this research was presented at the annual meeting

Acknowledgements

The authors thank O Schwartz for help in animal care, and M Shayit, MM Myers, H Shair, J Polan, CP Cramer, and SA Brunelli for discussion of portions of the current data. Also M Schroeder, Y Stern, O Malkesman and Y Braw are thanked for their assistance.

A portion of this research was supported by a grant from the Israel Foundation Trustees to AW. Research in Dr. Weller's Lab is partially supported by The Paula Rich Center, BIU, Israel.

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