Vagally mediated inhibition of acoustic stress-induced cortisol release by orally administered kappa-opioid substances in dogs.
The effects of oral vs. iv administration of kappa- and mu-opioid agonists on plasma cortisol release induced by acoustic stress (AS) were evaluated in fasted dogs with an implanted jugular catheter. AS was induced by 1 h of music (less than or equal to 86 decibels) played through earphones and was accompanied by a 382% maximal rise in plasma cortisol after 15-30 min. Administered orally 30 min before the AS session, both U-50488 (0.1 mg/kg) and PD 117-302 (0.05 mg/kg) significantly (P less than or equal to 0.01) decreased (by 71.2% and 80.9%, respectively) the maximal increase in plasma cortisol induced by AS, while bremazocine, morphine, as well as iv administration of U-50488 at similar doses were ineffective. The effects of U-50488 and PD 117-302 orally administered (0.1 mg/kg) on the hypercortisolemia induced by AS were abolished by pretreatment with iv naloxone (0.1 mg/kg) or MR 2266 (0.1 mg/kg). Naloxone given alone significantly (P less than 0.01) increased basal plasma cortisol, without affecting cortisol increase induced by AS. Vagotomy abolished the effects of orally administered U-50488 on the AS-induced increase in plasma cortisol. Neither U-50488 nor PD 117302 (0.1 mg/kg, orally) reduced the increase in plasma cortisol induced by intracerebroventricular administration of ovine CRF (100 ng/kg). It is concluded that kappa- but not mu-opioid agonists are able to inhibit the stimulation of the hypothalamo-pituitary-adrenocortical axis induced by AS by acting selectively on peripheral kappa-receptors located in the wall of the proximal gut. This action is neurally mediated through afferent vagal fibers affecting central nervous system release of CRF induced by a centrally acting stressor.
Bueno
L
L
Department of Pharmacology, INRA, Toulouse, France.
Gue
M
M
Fargeas
M J
MJ
Alvinerie
M
M
Junien
J L
JL
Fioramonti
J
J
D000284:Administration, Oral; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D004285:Dogs; D004723:Endorphins / Q000008:administration & dosage / Q000494:pharmacology*; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D001575:Benzomorphans; D004723:Endorphins; D009270:Naloxone; C027247:MR 2266; D006854:Hydrocortisone