Behavioral and endocrine adaptation, and up-regulation of NPY expression in rat amygdala following repeated restraint stress.

A single 1 h restraint increases experimental anxiety in the elevated plus-maze through actions within the amygdala, while intra-amygdala administration of neuropeptide Y (NPY) has the opposite effect. Endogenous amygdala NPY expression is suppressed by single restraint, providing a possible mechanism for the anxiety-promoting action of this stressor. Here, we examined whether repeated stressor exposure might lead to an adaptation (habituation or sensitization) with regard to plus-maze behavior and glucocorticoid response, and whether this might be accompanied by altered effects of the stressor on NPY expression. Following repeated restraint (1 h/day, 9-10 days), neither an anxiogenic-like effect of the stressor nor a glucocorticoid response were present. This behavioral and endocrine adaptation was accompanied by an up-regulation of prepro-NPY mRNA and NPY peptide in amygdala but not in hypothalamic or cortical extracts, an effect opposite to that previously seen after a single restraint session. Thus, an up-regulation of NPY expression in the amygdala complex may be an adaptive mechanism recruited to cope with a repeated stressor.