Chronic naloxone treatment induces supersensitivity to a mu but not to a kappa agonist at the hypothalamus-pituitary-adrenocortical axis level.

It has been demonstrated previously that chronic treatment with opioid antagonists enhances the potency of opioid agonists (supersensitivity) and produces an increase in brain opioid binding sites (up-regulation). The objective of the present study was to examine whether chronic blockade of mu-opioid receptors with naloxone would produce functional supersensitivity to the action of selective mu- and/or kappa-opioid agonists, within the hypothalamus-pituitary-adrenocortical axis. Naloxone (0.5 mg/kg/hr) was infused s.c. to Sprague-Dawley rats via osmotic minipumps for 7 days. The increase in plasma corticosterone produced by 30 mg/kg i.p. of morphine in control rats was shown to be significantly higher in naloxone-pretreated rats, 24 hr after pump removal. Furthermore, in naloxone-pretreated rats, 10 mg/kg i.p. of morphine significantly increased corticosterone levels 24 hr after naloxone was withdrawn, whereas in control rats the concentration of corticosterone increased first after the 30-mg/kg dose. No supersensitivity could be detected to the stimulating action on corticosterone release of U-50,488H (trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidynyl)cyclohexyl]ben zeneacetamide methane sulfonate; 1 or 15 mg/kg i.p.), 1 day after cessation of naloxone treatment. These data suggest that chronic blockade of the mu receptor with naloxone may induce a functional supersensitivity to the effects of mu- but not to those of kappa-agonists on the hypothalamus-pituitary-adrenocortical axis.

• Publication year

  1993

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1993-07-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0022-3565(25)39555-8PMID 8396640
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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