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Effects of specific mu and kappa opiate tolerance and abstinence on hypothalamo-pituitary-adrenal axis secretion in the rat.

Publication ,  Journal Article
Ignar, DM; Kuhn, CM
Published in: J Pharmacol Exp Ther
December 1990

Chronic administration of opiates to rats results in HPA axis tolerance and abstinence-induced hypersecretion. The effects of specific mu and kappa tolerance and withdrawal on the functional secretion of the HPA axis were evaluated in this study. Adult male rats were injected s.c. twice daily with saline, morphine or U50,488 for 5 days. Serum adrenocorticotrophic hormone (ACTH) or corticosterone (CS) were determined by radioimmunoassay as measures of HPA axis function. Tolerance to morphine (10 mg/kg) and U50,488 (1 mg/kg), but no cross-tolerance, was observed suggesting the development of mu- or kappa-specific tolerance, respectively. Tolerance does not occur at the pituitary or adrenal levels after these paradigms because ACTH and CS responses to exogenous corticotropin-releasing factor and ACTH, respectively, were not attenuated. CS secretion in response to novelty stress was not affected by either chronic opiate treatment, but the circadian variation of CS levels was slightly blunted after chronic morphine. In contrast, the elevation of CS secretion by quipazine (0.5 mg/kg) and physostigmine (0.1 mg/kg) was attenuated after chronic U50,488, but not morphine administration. Both spontaneous and antagonist-precipitated withdrawal from morphine, but not U50,488, resulted in elevation of CS levels. Low doses of morphine suppressed morphine abstinence-induced CS hypersecretion, whereas, U50,488 and clonidine had no effect. In conclusion, alterations of HPA axis function occur during chronic mu or kappa opiate administration that are receptor-specific and involve multiple neural controls of the HPA axis.

Duke Scholars

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

December 1990

Volume

255

Issue

3

Start / End Page

1287 / 1295

Location

United States

Related Subject Headings

  • Substance Withdrawal Syndrome
  • Stress, Physiological
  • Serotonin
  • Receptors, Opioid, mu
  • Receptors, Opioid, kappa
  • Receptors, Opioid
  • Rats, Inbred Strains
  • Rats
  • Pyrrolidines
  • Pituitary-Adrenal System
 

Citation

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Ignar, D. M., and C. M. Kuhn. “Effects of specific mu and kappa opiate tolerance and abstinence on hypothalamo-pituitary-adrenal axis secretion in the rat.J Pharmacol Exp Ther 255, no. 3 (December 1990): 1287–95.
Ignar, D. M., and C. M. Kuhn. “Effects of specific mu and kappa opiate tolerance and abstinence on hypothalamo-pituitary-adrenal axis secretion in the rat.J Pharmacol Exp Ther, vol. 255, no. 3, Dec. 1990, pp. 1287–95.

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

December 1990

Volume

255

Issue

3

Start / End Page

1287 / 1295

Location

United States

Related Subject Headings

  • Substance Withdrawal Syndrome
  • Stress, Physiological
  • Serotonin
  • Receptors, Opioid, mu
  • Receptors, Opioid, kappa
  • Receptors, Opioid
  • Rats, Inbred Strains
  • Rats
  • Pyrrolidines
  • Pituitary-Adrenal System