Elsevier

Life Sciences

Volume 24, Issue 9, 26 February 1979, Pages 771-781
Life Sciences

Effects of hypophysectomy and ACTH on opiate tolerance and physical dependence

https://doi.org/10.1016/0024-3205(79)90360-6Get rights and content

Abstract

In opiate-naive hypophysectomized rats, the enhanced potency of parenterally injected morphine was almost completely normalized by chronic ACTH in doses that maintained adrenal weight. Following morphine pellet implantation, the amount of morphine required for antinociception, catalepsy, and colonic temperature effects in tolerant rats was identical among hypophysectomized and sham-operated rats whether or not chronic ACTH was administered. However, brain levels of morphine were greater in tolerant, hypophysectomized rats, an effect blocked by chronic ACTH. Hypophysectomy thus appears to enhance the magnitude of tolerance development by a mechanism that is reversed by doses of ACTH that maintain adrenal weight. On the other hand, in sham-control rats this dose and schedule of ACTH were without effect on morphine potency in opiate-naive or tolerant rats or on brain levels of morphine. In general, hypophysectomy and/or ACTH did not modify the intensity of abstinence signs following naloxone-precipitated withdrawal. Therefore, little evidence was obtained to suggest a direct, commanding role of the pituitary in chronic opiate effects. Instead, a secondary adrenal involvement may be important.

References (32)

  • W. Krivoy et al.

    Eur. J. Pharmacol.

    (1974)
  • E. Zimmermann et al.

    Drug Effects on Neuroendocrine Regulation

  • L.-F. Tseng et al.

    Biochem. Biophys. Res. Commun.

    (1977)
  • G. Queen et al.

    Biochem. Biophys. Res. Commun.

    (1976)
  • G.F. Gebhart et al.

    Eur. J. Pharmacol.

    (1972)
  • L. Terenius

    Eur. J. Pharmacol.

    (1976)
  • E. Zimmermann et al.
  • W.A. Krivoy et al.
  • D. De Wied et al.

    Psychopharm.

    (1976)
  • J.M. Van Ree et al.

    Life Sci.

    (1976)
  • E. Wei et al.

    Science

    (1976)
  • L.-F. Tseng et al.
  • J. BLASIG and A. HERZ, Naunyn-Schmiedeberg's Arch. Pharmacol. (in...
  • Y.P. Loh et al.

    J. Gen. Physiol.

    (1977)
  • R.E. Mains et al.
  • R. Guillemin et al.

    Science

    (1977)
  • Cited by (0)

    Present address: Department of Medical Neurosciences, Division of Neuropsychiatry, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C. 20012.

    View full text