This study thus showed that, although the low-anxiety strains (SHR) and high-anxiety strains (LEW) vary in terms of some aspects of 5-HT function, key anxiety-related components of central serotonergic systems (such as the 5-HT1A autoreceptors) were no different. Of course, this result could be explained by the fact that the tools used at that time were insufficient or not sensitive enough to thoroughly explore central serotonergic activity. However, we should not Inhibitors,research,lifescience,medical dismiss the possibility that the basal conditions

under which we performed our study were not the most adequate to reveal strain differences, if any, in central serotonergic systems. In keeping with such a hypothesis, we then explored these systems under stimulated conditions. Social stress by repeated defeat has been shown to be endowed with neuroendocrine and behavioral effects that render this stress model useful to identify adaptive mechanisms.14,15 Among these mechanisms,

Inhibitors,research,lifescience,medical those Inhibitors,research,lifescience,medical related to central serotonergic systems (eg, hippocampal 5-HT1A and cortical 5-HT2A receptors)16 have been particularly underlined. but Nonetheless (i) how the neuroendocrine and behavioral effects of social stress are affected by the genetic status of the animal, and (ii) how this status affects the relationships between central serotonergic systems and adaptive processes, have not been studied.

We thus analyzed the effects of repeated defeat by Inhibitors,research,lifescience,medical Long-Evans resident rats (30 min of social defeat followed by 14-18 h of sensory contact with the certainly aggressor daily for 7 days) upon the psychoneuroendocrine profile of SHR and LEW.17 Repeated defeat time-dependently decreased body weight growth and food intake in both strains, but these decreases were more severe and longer-lasting in the LEW strain. This strain-dependent difference could not be accounted for by differences in physical contacts with the resident rats because the number of Inhibitors,research,lifescience,medical attacks and their latency throughout the stress period were similar for the two strains. When exposed to an elevated plus-maze test of anxiety, the unstressed LEW entered the open Drug_discovery arms less than their SHR counterparts, thus confirming above findings. This difference was amplified by social stress, which increased anxiety-related behaviors in LEW only. In the forced swimming test, LEW spent more time immobile than SHR, with stress increasing immobility in a strain-independent manner. In addition to the metabolic changes described above, the activity of the hypothalamo-pituitary-adrenal (HPA) axis was slightly stimulated in a strain-independent manner by the stressor, as indicated by increased corticosterone levels and adrenal weights, and decreased thymus weights.