Involvement of μ-opioid receptors in the modulation of pituitary-adrenal axis in normal and stressed rats

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Abstract
The availability of the most selective, high-affinity, natural opioid agonists for μ-receptors (dermorphin-DM) and δ-receptors (deltorphin-DT) has provided the possibility for in vivo studying of the role of acute and chronic activation of μ-and δ-opioid receptors on the functional activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, both in basal conditions and in response to an acute stress in adult male rats. Plasma corticosterone (CS) and ß-endorphin-like-immunoreactivity (ß-EP-LI) levels were measured by specific radioimmunoassays before and after 5 and 30 minutes from the exposure to cold (3±0.5 C) water and forcing them to swim for 10 minutes (acute cold swimming stress). Acute administration of DM, the specific μ-receptor agonist, enhanced basal and stress induced plasma levels of CS and ß-EP-LI. These effects were antagonized by pretreatment with nalox-one, specific μ-opioid receptor antagonist, but not by naltrindole, a δ-opioid receptor antagonist. Long-term administration of DM did not alter resting plasma levels of CS and ß-EP-LI, but significantly reduced stress-induced increase of these hormones. Both the acute and chronic administration of the DT, highly selective δ-opioid receptors agonist, failed to modify resting and stress induced hormone levels. Our present data show that DM throughout μ-opioid receptors, but not DT, modulates the response of HPA axis to acute stress in rats, increasing or decreasing the release of CS and ß-EP-LI when acutely or chronically administered, respectively.