Molecular and neural correlates of adolescent depression in females A study in the Wistar Kyoto rat

Abstract

The main aim of this research work was to establish an animal model of adolescent depression based on diagnostic statistical manual V (DSM V) criteria with face, construct and predictive validities. Adolescence constitutes a sensitive critical period of brain and behavioural development. Due to developing limbic brain areas, maturing neurotransmitter pathways and continued development of the hypothalamus-pituitary-adrenal axis, the adolescent brain is extremely vulnerable. Furthermore, it has been shown that administration of adult antidepressants induces suicidal behaviour in adolescents. Genetic predisposition to depression coupled with extraneous stressors and puberty-associated flux in steroidal hormones increases the susceptibility, particularly in females. Study of pathophysiology of depression at the preclinical level is skewed towards males. To address this void, the Wistar Kyoto rat (WKY) female rat model was used in this study. WKY is a line derived from Wistar rats and has been suggested as a putative model for childhood depression in males. The study was carried out at neurobehavioral and neurochemical levels by employing paradigms such as elevated plus maze (EPM), forced swim test (FST), sucrose preference test (SPT) for anhedonia, social interaction test (SI), novelty suppressed feeding (NSF) to screen for anxiety- and depressive-like profiles and HPLC for central and peripheral monoamine/metabolite profiles and turnovers. All the studies were carried out in comparison with age-matched female Wistar rats. Early, mid- and late adolescence and young adulthood were considered as separate time windows. Further to test the double-hit hypothesis, the endogenous model was subjected to subchronic and chronic stressors. newline