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.

Keywords: Adolescence; Anhedonia; Anxiety; Childhood depression; Females; Ultrasonic vocalizations.