Pituitary-adrenocortical response to acute and chronic administration of U-50,488H in the rat.
K-opioid substances have been shown to stimulate and/or depress the HPA activity. The objective of this study was to determine the effects of the acute and chronic administration of U-50,488H, a k-opioid receptor agonist, on the pituitary-adrenocortical activity in the rat. The acute administration of U-50,488H (25 mg/kg i.p.) produced a hypothermic effect and an increase in plasma levels of B-END-LI and cortisol, effects which were prevented by naloxone (3 mg/kg s.c.). Chronic administration of U-50,488H twice a day for 4 days resulted in a decrease in basal plasma levels of B-END-LI and cortisol and in the development of tolerance to its neuroendocrine and hypothermic effects. In rats made tolerant to U-50,488H, naloxone precipitated hypothermia (which is an index of opiate dependence in rats), whereas no changes in plasma B-END-LI and cortisol levels were seen. These data suggest that k receptors may be involved in the regulation of pituitary-adrenocortical activity in physiological conditions and during opiate abuse. On the other hand, U-50,488H induced only negligible dependence in rats, which was not morphine-like.
Milanés
M V
MV
Department of Physiology and Pharmacology, University School of Medicine, Murcia, Spain.
Gonzalvez
M L
ML
Fuente
T
T
Vargas
M L
ML
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000302:Adrenal Cortex / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D001615:beta-Endorphin / Q000097:blood
D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D006854:Hydrocortisone