Elsevier

Biological Psychiatry

Volume 59, Issue 1, 1 January 2006, Pages 17-23
Biological Psychiatry

Original article
Two Different Putative Genetic Animal Models of Childhood Depression

https://doi.org/10.1016/j.biopsych.2005.05.039Get rights and content

Background

In an attempt to model childhood depression, we examined whether existing genetic animal models of depression in adult rats are also valid in prepubertal rats.

Methods

Two different “depressed” rat lines were studied: the Flinders Sensitive Line (FSL) and their controls, Sprague-Dawley (SD); and the Wistar Kyoto (WKY) line and their controls, Wistar. We hypothesized that male prepubertal FSL and WKY rats would show increased swim test immobility and different patterns of social play and of basal plasma levels of corticosterone and adrenocorticotropic hormone (ACTH) compared with control rats.

Results

Prepubertal FSL and WKY rats exhibited significantly longer duration of immobility than control rats in the swim test. The FSL rats demonstrated significantly higher levels of social play behaviors and lower levels of corticosterone and ACTH compared with SD control rats, whereas WKY rats demonstrated significantly lower levels of social play behaviors and higher plasma levels of corticosterone and ACTH compared with Wistar control rats.

Conclusions

The results might suggest that prepubertal FSL and WKY rats are both putative genetic animal models of childhood depression, exhibiting separate patterns and symptoms of childhood depression.

Section snippets

Swim Test

The forced swim test, developed by Porsolt et al (1977), has become a widely used paradigm for studying stress responses and for screening antidepressant drugs (Abel 1993; but see Kawashima et al 1986). Prolonged immobility duration in this test is regarded as behavioral despair, an animal analogue of human depression. The general procedure in this paradigm is to immerse rats or mice in a cylinder of water from which there is no escape. Twenty-four hours later, rats are retested for 5 min.

Animals

Nulliparous SD and FSL female rats were mated with male rats from the same line in their breeding colonies, in the Developmental Psychobiology Laboratory at Bar-Ilan University, Ramat-Gan, Israel. Both lines were likely to be inbred because of the relatively small number of original parents. Wistar Kyoto (WKY; Harlan, Jerusalem, Israel) and Wistar (Harlan, Indianapolis, Indiana) prepubertal rats were supplied by Harlan for the behavioral tests (we have since performed additional studies in our

Results

The immobility data are presented in Figure 1, Figure 2. As evident from the figures, both FSL and WKY lines exhibited significantly longer immobility duration in the swim test compared with their control lines [SD–FSL: F(1,22) = 25.77, p < .05; Wistar–WKY: F(1,28) = 59.43, p < .01]. The FSL rats weighed significantly less (mean ± SEM = 101.1 ± 3.48 g) than SD rats (129.3 ± 4.34 g) [F(1,22) = 25.772, p < .01], and WKY rats weighed significantly less (131.6 ± 2.65 g) than Wistar control rats

Discussion

Childhood depression has received attention as a significant clinical phenomenon only relatively recently, and was almost completely ignored until the 1970s. The dramatic change in interest taken by child psychiatrists in affective disorders has arisen from two major areas of advance in adult psychiatry: diagnostic theory and the advances in the biochemical, genetic, and therapeutic understanding of affective disorders in adults (Apter and Tyano 1984). These changes facilitated recognition that

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