Role of endogenous opioid system in the regulation of the stress response

1. Numerous studies and reviews support an important contribution of endoge nous opioid peptide systems in the mediation, modulation, and regulation of stress responses including endocrine (hypothalamo-pituitary-adrenal, HPA a xis), autonomic nervous system (ANS axis), and behavioral responses. Althou gh several discrepancies exist, the most consistent finding among such stud ies using different species and stressors is that opioids not only diminish stress-induced neuroendocrine and autonomic responses, but also stimulate these effector systems in the non-stressed state. 2. A distinctive feature of the analgesic action of opioids is the blunting of the distressing, affective component of pain without dulling the sensat ion itself. Therefore, opioid peptides may diminish the impact of stress by attenuating an array of physiologic responses including emotional and affe ctive. 3. The widespread distribution of enkephalin (ENK) throughout the limbic sy stem (including the extended amygdala, cingulate cortex, entorhinal cortex, septum, hippocampus, and the hypothalamus) is consistent with a direct rol e in the modulation the stress responses. 4. The predictability of stressful events reduces the impact of a wide rang e of stressors and ENK appears to play an important role in this process. T herefore, ENK and its receptors could represent a major modulatory system i n the adaptation of an organism to stress, balancing the response that the stressor places on the central stress system with the potentially detriment al effects that a sustained stress may produce. Chronic neurogenic stressor s will induce changes in specific components of the stress-induced ENKergic system, including ENK, delta- and mu -opioid receptors. 5. This review presents evidences for adaptive cellular mechanisms underlyi ng the response of the central stress system when assaulted by repeated psy chogenic stress, and the involvement of ENK in these processes.