Divergent maternal behavioral patterns in two genetic animal models of depression.

Maternal behavior was examined in Flinders Sensitive-Line (FSL) and Wistar-Kyoto (WKY) rats, two different genetic animal models of depression. Behavioral patterns were assessed by undisturbed observations in the nest [Post-Partum Days (PPD) 4 and 9] and post-disturbance observations ("retrieval tests") on PPD 10. Litters were randomly allocated to a mild chronic-stress condition (limiting available bedding between PPD 2 and 9) or a standard rearing condition. The findings indicated that FSL dams did not differ from control dams in the undisturbed observations. However, in the post-disturbance observations FSL dams exhibited less pup-directed behaviors, a shorter latency to first pup carrying/retrieval and more self-directed behaviors than controls (the latter effect only in dams' interaction with whole litter). In contrast, WKY dams performed more pup-directed activities (e.g., nursing and licking) and less self-directed activities in both the undisturbed and post-disturbance observations (in both dams' interaction with single-pup and with the whole-litter) compared to controls. Accordingly, WKY dams exhibited a shorter latency for first pup-licking bout (in both post-disturbance observations). The early life mild chronic-stress used in the study ('limited-bedding') had a minor effect on the dams' behavior. Overall, the study investigated for the first time the maternal behavior of WKY dams and suggests that these dams show an almost opposite behavioral pattern to that of FSL dams. The results are discussed with regard to earlier findings in the FSL strain and behavioral patterns documented in depressed human mothers.

A cross-fostering study in a genetic animal model of depression: maternal behavior and depression-like symptoms.

Connections between maternal behavior and childhood depression were examined by using a "genetic animal model"; Flinder Sensitive Line--(FSL) rats, and cross-fostering the offspring with the control strain, Sprague Dawley (SD) rats. The control procedure was "in-fostering", where the foster dam and her pups were from the same strain. Contribution of pups' characteristics/genotype to maternal behavior was examined. After weaning, we measured male offspring's body weight, immobility in the swim test, and basal corticosterone (CORT) and adrenocorticotropin (ACTH) levels at the prepubertal age of 35 days. While maternal behavior (of "depressive-like" dams and their controls) was not altered significantly by the pups' strain, the adoption procedure per se appeared to have more adverse effects on "depressive-like" symptoms of the SD prepubertal rats than on the FSL pups. Nevertheless, the combination between abnormal maternal behavior and genetic predisposition affected the hormonal stress responses of the offspring in a more severe manner than genetic predisposition or abnormal maternal behavior per se.

Stress and pain responses in rats lacking CCK1 receptors.

UNLABELLED: CCK involvement in stress- and pain-responsiveness was examined by studying the behavior of infant (11-12-days-old) and adult OLETF rats that do not express CCK1 receptors. Infant odor- and texture-preferences were also assessed. We hypothesized that OLETF rats will show behavioral patterns similar to those previously observed after CCK1 antagonist administration. Rate of separation-induced ultrasonic vocalization was significantly greater in OLETF compared to controls, in two separate studies. Infant pups of the two strains did not differ in odor- and texture-preference tests. OLETF rats showed consistently longer hot-plate paw-lift (as infants, in two separate studies) and paw-lick (as adults) latencies. SUMMARY: OLETF pups vocalized in isolation more than controls and showed relative hypoalgesic responses, evident also in adulthood, in concordance with the pharmacological literature.

Anxiety-like behaviors in pre-pubertal rats of the Flinders Sensitive Line (FSL) and Wistar-Kyoto (WKY) animal models of depression.

Animal models have been used in understanding the neuro-biological basis of depression and predicting successful treatment strategies. The current study focused on two genetic models of depression, the Flinder's Sensitive Line (FSL) and Wister-Kyoto (WKY). Our laboratory showed depressive symptomatology in pre-pubertal WKY and FSL rats, and the current study focused on the strains' anxiety-like traits. Since human depression-anxiety comorbidity is very common at young ages, it is essential to establish whether FSL and WKY pre-pubertal rats also exhibit such comorbidity. In addition, the effect of different rearing environments was studied using a mild chronic-stress condition (limiting available bedding between post-natal days 2-9). Two well-validated tests of anxiety, the open-field and elevated plus-maze, were used on 40-day-old pups. FSL pups exhibited lower anxiety-like behavior when compared to controls, in traditional open-field and plus-maze measures. A different pattern was observed in the WKY strain, which exhibited heightened anxiety-like behaviours in the FSL strain and affecting WKY's body-weight. Overall, the findings indicate differential expression of anxiety in pre-pubertal rats belonging to the 'depressed' strains, suggesting that these strains may be suitable for modelling different sub-groups of depression at young ages.

Reward and anxiety in genetic animal models of childhood depression.

One of the most important criteria for major depressive disorder in adults and in children and adolescents as well, is the loss of interest in or pleasure from typically enjoyable experiences or activities: anhedonia. Anxiety is frequently co-morbid with depression. We examined reward and anxiety in genetic animal models of childhood depression. Two different "depressed" lines were studied: the Flinders Sensitive Line (FSL) and their controls, Sprague-Dawley (SD) rats and the Wistar Kyoto (WKY) line and their controls, Wistar rats. Recently, we found that prepubertal rats (about 35 days old) from these lines exhibited increased immobility in the swim test, and abnormal social play observed after 24-h isolation. We hypothesized that FSL and WKY prepubertal rats will further show anhedonia in two different behavioral assays: the conditioned place preference test (CPP), examining the rewarding aspect of social interaction and the saccharin preference test. Behavior in the open field paradigm and freezing behavior in the CPP apparatus were also used as measures of anxiety. WKY, but not FSL prepubertal rats, consumed less of the saccharin solution compared to their control line. FSL, and WKY prepubertal rats found social interaction to be rewarding to a similar extent as their control lines, in the CPP test. Only the WKY rats showed anxiety in behavior in the open field and freezing behavior in the CPP paradigm. The results suggest that WKY prepubertal rats are anxious and sensitive to stress-induced anhedonia, while FSL prepubertal rats exhibit none of these symptoms.