Two Wistar rat lines, selectively bred for high-anxietyrelated behavior (HAB) and low-anxiety-related behavior (LAB) in the elevated plus-maze test, were tested for the susceptibility of their behavioral characteristics to anxiolytic treatment and for their endocrine and physiological reactivity to different stressors. Injection of 1mg/kg diazepam failed to affect line differences in coping strategy but resulted in a marked (20-fold) Genetic factors contribute to the high interindividual variability in type and/or intensity of the behavioral, neuroendocrine, and physiological stress responses observed in various species, including humans and laboratory rats (Boissy 1995;Clément et al. 1997;Cools et al. 1990;Curé and Rolinat 1992;Prasad et al. 1996;Spanagel et al. 1995;Tesser 1993;Zuckerman 1993). This fact has been used as the basis for selective bidirectional breeding programs from which strains and lines differing in their behavioral and/or neuroendocrine reFrom the Max Planck Institute of Psychiatry, Munich, Germany. Address correspondence to: Dr. R. Landgraf, Max Planck Institute of Psychiatry, Kraepelinstr. 2, 80804 Munich, Germany.Received January 15, 1997; revised March 25, 1998; accepted April 16, 1998. 382 G. Liebsch et al. N EUROPSYCHOPHARMACOLOGY 1998 -VOL . 19 , NO . 5 sponses to environmental challenges have emerged (Brush 1991;Castanon and Mormède 1994;Cools et al. 1993;Gentsch et al. 1988;Walker et al. 1992). Recently, we reported the establishment of two Wistar rat lines selectively bred for differing behavioral performances in the elevated plus-maze test, now termed high-anxiety-related behavior (HAB) and low-anxiety-related behavior (LAB) lines, respectively ). This animal model of inborn anxiety provides the advantage of avoiding conditioned stimuli that by themselves are likely to trigger behavioral, neuroendocrine, and physiological alterations. Interestingly, the HAB and LAB animals also prefer different coping strategies in a forced swim test ), pointing toward a link between anxiety and coping with stressful situations.The elevated plus-maze test is based on the creation of a conflict between the exploratory drive of a rat and its innate fear of open, exposed areas. It is one of the most widely used nonconditioned animal models of anxiety and has been extensively validated pharmacologically and ethologically (Dawson and Tricklebank 1995;Pellow 1986;Pich et al. 1993). However, various clinically effective anxiolytic substances often yield contradictory results when administered to "normal" unstressed rats in this test (Griebel 1995;Rodgers et al. 1997), indicating that-in parallel to the situation in humans (Green and Hodges 1991; Lader 1991)-the efficacy of an anxiolytic may depend upon the animal's basal level of anxiety. To test this prediction and to characterize further our breeding lines, in the first experiment, male rats from the HAB and LAB lines were injected with a classical anxiolytic, diazepam, and submitted to a plus-maze test and a forced swim test to assess the e...