INVOLVEMENT OF MU-OPIOID RECEPTORS IN THE MODULATION OF PITUITARY-ADRENAL AXIS IN NORMAL AND STRESSED RATS

The availability of the most selective, high-affinity, natural opioid agonists for mu-receptors (dermorphin-DM) and delta-receptors (deltorp hin-DT) has provided the possibility for in vivo studying of the role of acute and chronic activation of mu-and delta-opioid receptors on th e functional activity of the hypothalamus-pituitary-adrenocortical (HP A) axis, both in basal conditions and in response to an acute stress i n adult male rats. Plasma corticosterone (CS) and beta-endorphin-like- immunoreactivity (beta-EP-LI) levels were measured by specific radioim munoassays 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 mu-recepto r agonist, enhanced basal and stress induced plasma levels of CS and b eta-EP-LI. These effects were antagonized by pretreatment with naloxon e, specific mu-opioid receptor antagonist, but not by naltrindole, a d elta-opioid receptor antagonist. Longterm administration of DM did not alter resting plasma levers of CS and B-EP-LI, but significantly redu ced stress-induced increase of these hormones. Both the acute and chro nic administration of the DT, highly selective delta-opioid receptors agonist, failed to modify resting and stress induced hormone levels. O ur present data show that DM throughout mu-opioid receptors, but not D T, modulates the response of HPA axis to acute stress in rats, increas ing or decreasing the release of CS and beta-EP-LI when acutely or chr onically administered, respectively.