Born to be Anxious: Neuroendocrine and Genetic Correlates of Trait Anxiety in HAB Rats

Abstract

This review summarises behavioural, neuroendocrine, and genetic characteristics of Wistar rats bred for either high (HAB) or low (LAB) anxiety-related behaviour. Compared to LABs, HAB animals show signs of extreme trait anxiety in a variety of behavioural tests; they further prefer passive coping strategies, indicative of a genetically linked depression-like behaviour, and show signs of increased stress vulnerability. All behavioural parameters associated with trait anxiety are robust and consistent. Resembling psychiatric patients, HAB rats respond to exposure to ethologically relevant stressors with a hyper-reactivity of the hypothalamic-pituitary-adrenal axis and show a pathological outcome of the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) challenge test. Experimental evidence indicates that over-expression and -release of vasopressin in the hypothalamic paraventricular nucleus is responsible for these behavioural and neuroendocrine phenomena, making the neuropeptide gene a candidate gene of trait anxiety/depression. Indeed, preliminary molecular genetic approaches succeeded in identifying polymorphisms in the promoter structure of the vasopressin gene. This may have implications for understanding the molecular basis for individual variations in trait anxiety and for psychopathology.