The selective breeding of Wistar rats for high (HAB) versus low (LAB) anxiety-related behaviour resulted in two rat strains which have been validated as a suitable animal model for studying neurochemical and genetic mechanisms underlying anxiety- and depression-related disorders. The robust differences in the anxiety phenotype are accompanied by alterations in neuroendocrine and neuronal stress-responsiveness to various stimuli, and in relevant brain neurotransmitter systems including arginine vasopressin (AVP), CRF and serotonin, and by impaired hippocampal neurogenesis. Manipulation of the endogenous vasopressin or oxytocin systems reveals their significant involvement as neuromodulators of anxiety behaviour in HAB rats.

HAB and LAB rats also provide an excellent model for studying interactions between early environmental factors (i.e. early life stress: prenatal stress, maternal separation) and the genetic predisposition for either high or low stress susceptibility. Thus, differential, partly opposite effects of prenatal or postnatal stress on adult emotionality, stress coping, neuropeptide expression patterns within the hypothalamus or hippocampal cell survival have been found in adult HAB and LAB rats.

Finally, selection for low trait anxiety in LAB rats goes along with the development of high intermale aggression during the resident-intruder test, and with a generally high neuroendocrine and neuronal response to social stimuli. Therefore, LAB males may develop as a promising animal model for studying neurobiological mechanisms of pathological aggression and its link to the genetically determined level of anxiety.