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

Abstract

The availability of the most selective, high-affinity, natural opioid agonists for mu-receptors (dermorphin-DM) and delta-receptors (deltorphin-DT) has provided the possibility for in vivo studying of the role of acute and chronic activation of mu- and delta-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 beta-endorphin-like-immunoreactivity (beta-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 mu-receptor agonist, enhanced basal and stress induced plasma levels of CS and beta-EP-LI. These effects were antagonized by pretreatment with naloxone, specific mu-opioid receptor antagonist, but not by naltrindole, a delta-opioid receptor antagonist. Long-term administration of DM did not alter resting plasma levels of CS and beta-EP-LI, but significantly reduced stress-induced increase of these hormones. Both the acute and chronic administration of the DT, highly selective delta-opioid receptors agonist, failed to modify resting and stress induced hormone levels. Our present data show that DM throughout mu-opioid receptors, but not DT, modulates the response of HPA axis to acute stress in rats, increasing or decreasing the release of CS and beta-EP-LI when acutely or chronically administered, respectively.

The role of endogenous opioids in neurohypophysial and hypothalamo-pituitary-adrenal axis hormone secretory responses to stress in pregnant rats

“…We have now shown that, in pregnancy, the enhancing action of endogenous opioid on ACTH release in response to forced swimming, which is normally seen in virgins, is removed. The reduction in ACTH secretion in response to the stressor after naloxone in virgins is consistent with the findings of previous studies showing that opioid antagonists reduce ACTH and corticosterone secretion in response to a stressor in male rats (degli Uberti et al 1995). Naloxone is likely to be exerting its effects on the HPA axis via the hypothalamus (Wang et al 1996), and thus may affect hypothalamic-pituitary mechanisms through CRH release.…”

Effect of μ-opioids morphine and buprenorphine on the development of adjuvant arthritis in rats

“…Endogenous and exogenous opioids are also known to affect the hypothalamicpituitaryadrenocortical axis (HPA) with contrasting effects depending on the administration mode (acute cfchronic). For example, acute administration of morphine, to activate p-opioid receptors, increases the release of neurohormones, like corticosterone, from the HPA axis [38]. In contrast, chronic treatment with tx-opioid agonists results in a decreased responsiveness of the HPA axis to stress in rats (for review see [39]).…”

Chronic Pain Induces Anxiety with Concomitant Changes in Opioidergic Function in the Amygdala

“…Opioid analgesics and endogenous opioid peptides have a wide range of physiological and behavioral effects on pain perception, motivation, locomotion, regulation of intestinal motility, immunomodulation, thermo-regulation, neuroendocrine secretion, and rewarding effects (Pasternak, 1988;Mansour et al, 1988;Cahill et al, 2001). It is well known that endogenous opioid peptides are released in the central nervous system in response to stressful stimuli, and activation of m-opioid receptor plays an important role in stressful conditions (Kiritsy-Roy et al, 1986;degli Uberti et al, 1995). d-Opioid receptors have also been associated with anxiety and depression, since d-agonists reduced the immobility of rats in a forced swimming test (Broom et al, 2002).…”