This intrinsic conflict between the drive for exploration of a novel environment and the assessment of the threatening potential of nonfamiliar stimuli is exploited for the generation of standard methods of fear- and anxiety-based

stress induction.59 Conditioned anticipation of fearful experience is also a powerful tool for the induction Inhibitors,research,lifescience,medical of stress responses, and there is substantial overlapping of the anatomical substrates involved in unconditioned and conditioned fear. However, quantitative and, to a lesser degree, qualitative differences in the activation of distinct neural populations have been revealed,60 and the LHPA axis appears to have a crucial role in the emergence of conditioned fear. It should be mentioned that the degree of stress response resulting from the first (and, sometimes, also subsequent) exposure to experimental devices and procedures must be meticulously Inhibitors,research,lifescience,medical characterized and, if possible, minimized by handling, in order to avoid bias while see more measuring the “proper” outcome of a stress model. Models of social conflict and disruption Interactions within a cospecific group (population) are probably the most persistent source of stressful stimuli; Inhibitors,research,lifescience,medical however, in a colony of highly domesticated laboratory

animals their impact often remains unaccounted, especially when using them as subjects in stress experiments. The baseline characteristics and the response profiles Inhibitors,research,lifescience,medical of end points used for stress assessment may critically depend on the individual’s status within the rapidly formed social group hierarchy and/or his or her previous experience in this environment. Models based on social conflicts exploit either the aggravation of existing, or the de novo creation of, stressful interactions in the course of establishing and maintaining of hierarchic relationships Inhibitors,research,lifescience,medical of dominance or subordination. Specific conflict-producing

experimental settings, such as territory defense (resident-intruder paradigm, colony overcrowding), hierarchy formation (social defeat, visible burrow system), offspring protection, and social instability are comprehensively reviewed.61 These paradigms produce strong alterations in several indicators of the stress response and, upon chronic application, the outcome 17-DMAG (Alvespimycin) HCl may mimic the features of human pathological conditions. In rats there are pronounced sex differences in the liability to social stress, with females being generally refractory to paradigms of hierarchy formation, but responsive to conditions of social instability.62 Social isolation (solitary housing) has been considered an appropriate method for stress induction63; however, some caveats of this model merit consideration. Social isolation implies long-term deprivation of the familiar environment and, accordingly, immediate effects of separation can be ascribed to novelty and experimental procedures (eg, handling, restraint).