Abstract
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rats, 10 mg/kg i.p. of morphine significantly increased corticosterone levels 24 hr after naloxone was withdrawn, whereas in control rats the concentration of corticosterone increased first after the 30-mg/kg dose.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.
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