Anxiety‐ and depressive‐like profiles during early‐ and mid‐adolescence in the female Wistar Kyoto rat

Abstract

Approaches for the development of preclinical models of depression extensively use adult and male animals owing to the discrepancies arising out of the hormonal flux in adult females and adolescents during attainment of puberty. Thus the increased vulnerability of females towards clinical depression and anxiety-related disorders remains incompletely understood. Development of clinical models of depression in adolescent females is essential in order to evolve effective treatment strategies for adolescent depression. In the present study, we have examined the anxiety and depressive-like profiles in a putative animal model of childhood depression, the Wistar Kyoto (WKY) rat, during early adolescence (∼postnatal day 30) and mid-adolescence (∼postnatal day 40). Female adolescent WKY rats, tested on a series of behavioural tests modelling anxiety- and depressive-like behaviours with age-matched Wistars as controls, demonstrated marked differences during early adolescence in a strain- and age-specific manner. Anxiety indices were obtained from exposure to the elevated plus maze, where social communication vide 50-kHz ultrasonic vocalizations was also assessed, while immobility and other parameters in the forced swim test were screened for depressive-like profiles. Sucrose preference, used as a measure of anhedonia in animals, was lower in WKYs at both ages tested and decreased with age. Anxiety-related behaviours were prominent in WKY rats only during early adolescence. WKY female rats are anxious during early adolescence and exhibit anhedonia as a core symptom of depression during early- and mid-adolescence, thus indicating that inclusion of female animals in preclinical trials is essential and will contribute to gender-based approaches to diagnosis and treatment of adolescent depression in females.

Estrous Cycle Phase-Dependent Changes in Anxiety- and Depression-Like Profiles in the Late Adolescent Wistar-Kyoto Rat

“…Proestrus-estrus females were found to be less active in the FST, demonstrating an increased depression-like profile indicating that established pathways are modulated by hormones [3] . The results of increased learned helplessness or behavioral despair observed here in late adolescent WKYs was not evident in early and mid-adolescent WKY females when they were compared to the progenitor Wistar strain [17] . Whether the ovarian hormonal milieu enhances the observed stress response or as discussed earlier is masked in WKY remains to be established.…”

“…Water was filled up to 32 cm from the base with water temperature maintained between 25 and 28 ° C. FST was carried out as per the procedure previously described [34,35] with minor modifications [14,17] . The procedure consisted of 2 days of testing.…”

“…In the FST, the time spent by the animals in passive behavior (floating) called immobility, which was defined as the lack of motion of the whole body, and active behaviors (swimming and climbing) along with the latency to the first immobility were scored automatically in real time by the system during data acquisition. Ethovision settings that differentiated between immobility, swimming, and climbing behaviors have been validated manually [14,17,36] .…”

“…A common psychopathological pathway underlies the high comorbidity between depression and anxiety disorders [21] , though expression of some neuropeptide biomarkers could enable a differentiation between anxiety and depression [22] . Moreover, in our earlier study, no correlations were obtained between anxiety-and depression-related behaviours in WKY [17] , hinting at a probable separation of anxiety-and depression-related symptoms [23] . Core symptoms such as anhedonia and learned helplessness are not specific even in humans [24] .…”

“…Furthermore, most female studies have used adults [3] . Very few studies use adolescent females [17] ; most adolescent studies involving pups at 30-40 days of age (prepubertal) include both sexes [7,18] with no differences being shown between adolescents and adults [19] . However, sexually dimorphic gene expression differences exist prior to puberty with sex hormones acting as transcriptional regulators causing abundant gene expression differences between sexes [11] .…”