HAB/LAB rats: an animal model of extremes in trait anxiety and depression

Using an intra-strain, bidirectional selective breeding approach, Wistar rats were bred for either high (HAB) or low (LAB) anxiety-related behaviour on the elevated plus-maze and a variety of additional behavioural tests including black/white box, open field, modified hole board, social interaction and ultrasound vocalization. Increased adrenocorticotropic hormone (ACTH) and corticosterone secretion upon mild stressor exposure suggests a hyper-reactivity of the hypothalamo-pituitary-adrenocortical axis in HAB rats. Accordingly, the hypothalamic paraventricular nucleus (PVN) was found to express and release more vasopressin, an ACTH secretagogue, in HAB than LAB animals. Furthermore, compared to LAB rats, HABs prefer passive stress coping strategies, indicative of depression-like behaviour. The antidepressant paroxetine has been shown to normalize both depression-like indices and vasopressin over-expression in the PVN of HABs without inducing any effects in LABs. Based on behavioural and neuroendocrine phenotyping, the vasopressin gene is considered as a candidate gene of trait anxiety/depression. Indeed, its promoter structure in HAB, but not LAB, animals contains single nucleotide polymorphisms (SNPs) likely to underlie vasopressin over-expression as well as trait anxiety/depression. The vasopressin system might thus become a promising target for novel therapeutic strategies. (C) 2003 Elsevier B.V. All rights reserved.