NEUROENDOCRINE AXIS AND BEHAVIORAL STRESS

Integrated neuroendocrine activation is necessary to successfully overcome stressful events. Neuroendocrine activation, part of the well-known biologic phase of stress adaptative responses, is not aspecifically generated by the organism, however, due to the effects of numerous factors, in part also genetically determined. Growing evidence shows the relevance of subjective cognitive and emotional modulation elaborated in cortical and subcortical structures of the brain in determining different individual strategies of stress response. The nervous system, where all stressful stimuli exert their initial effects, is well documented to play a crucial role in the generation of adequate stress responses by correctly integrating endocrine and immune system functions to maintain homeostasis of the organism. The specific individual pattern of stress response is also determined by modulation of emotional influences, as previously hypothesized by Mason. Emo- tional structures are located mainly in the modular neuronal network represented by the limbic system. The hypothalamus, in particular, with its connections to both central and peripheral nervous structures, and neuroendocrine integrated systems represents the limbic module more properly concerned with the organization of motivated behavioral and endocrine responses. Other limbic modules related to the emotional network are the amygdala, the area where emotional or affective quality are attributed to motivationally relevant stimuli, and the septum, one of the structures involved in the inhibition or selection of behavioral responses. In humans, neocortex cognitive influences, however, operate a superimposed control of cognitive influences on emotional structures, with various reciprocal interrelationships. Both endocrine and immune systems, in turn, feed back to the brain by closely affecting nervous system plasticity, its development, and its functions during adult life and aging. The presence of hormones and hormonal receptors in brain areas other than those typically involved in the control of endocrine function, such as the hypothalamus, supports the hypothesis that brain represents a direct target of hormonal effects. These bidirectional neuroendocrine interactions, classified as experiential hormonal effects, contribute to modulate neuroendocrine responses after different kinds of stressors, including psychological stress. As hormonal experiential effects are part of the individual experience, subsequent stress adaptative responses are so extremely variable as to be hardly predictable, accounting also for the emergence of variable degrees of pathologic states related to chronic stress exposure. Neuroendo- crine axis activation may vary in different species, taking into account the varying relevance of intermediate lobe metabolism of the proopiomelanocortin molecule, whereas in the same species it may closely depend on the specific stressors employed or the duration of stress exposure until the generation of dissociated neuroendocrine activation in particular pathologic states. The neuroendocrine cascade following the application of emotional stress is generally similar to that determined by other physical stressors, and several models of socially hierarchically organized animals provide suitable examples for evaluating such mechanisms. In humans, mental stress is known to induce pronounced and reproducible activation of the sympathoadrenal system, with elevation of plasma epinephrine and norepinephrine concentrations and subsequent hemodynamic changes (i.e., heart rate increase) and metabolic consequences, such as an increase in adipose tissue lipolytic activity and a reduction in adipocyte glucose uptake activity. Nevertheless, behavioral