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Chronic administration of U50,488H fails to produce hypothalamo-pituitary-adrenal axis tolerance in neonatal rats.

Publication ,  Journal Article
Ignar, DM; Windh, RT; Kuhn, CM
Published in: Neuropharmacology
February 1992

The present study investigated the effect of chronic administration of a kappa opioid receptor agonist on the function of kappa and mu opioid, serotonergic and cholinergic regulation of secretion from the hypothalamo-pituitary-adrenal axis in neonatal rats. After chronic treatment with saline or U50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzeneacetamide methane sulfonate), a kappa opioid receptor agonist and subsequent pharmacological challenge, corticosterone (CS) in serum was determined. Kappa tolerance did not develop in pups treated on postnatal days 5-9 with increasing doses of U50,488H (0.5-2.5 mg/kg). When the rats were treated with the same chronic regimen of U50,488H at different stages of development from birth through weaning, only weanling rats became tolerant to U50,488H. In the absence of measurable kappa tolerance, the responses of corticosterone in serum to morphine, quipazine, a serotonin receptor agonist and physostigmine, an inhibitor of acetylcholinesterase, were attenuated in neonatal rats, treated with U50,488H. These studies suggest that kappa tolerance is more difficult to induce in developing rats than in adults and that regulation of the function of the hypothalamo-pituitary-adrenal axis by other neurotransmitter systems is altered by treatment with kappa opioid receptor agonists, even in the apparent absence of tolerance.

Duke Scholars

Published In

Neuropharmacology

DOI

ISSN

0028-3908

Publication Date

February 1992

Volume

31

Issue

2

Start / End Page

143 / 148

Location

England

Related Subject Headings

  • Rats, Inbred Strains
  • Rats
  • Quipazine
  • Pyrrolidines
  • Pituitary-Adrenal System
  • Physostigmine
  • Neurology & Neurosurgery
  • Morphine
  • Hypothalamo-Hypophyseal System
  • Drug Tolerance
 

Citation

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Ignar, D. M., Windh, R. T., & Kuhn, C. M. (1992). Chronic administration of U50,488H fails to produce hypothalamo-pituitary-adrenal axis tolerance in neonatal rats. Neuropharmacology, 31(2), 143–148. https://doi.org/10.1016/0028-3908(92)90024-j
Ignar, D. M., R. T. Windh, and C. M. Kuhn. “Chronic administration of U50,488H fails to produce hypothalamo-pituitary-adrenal axis tolerance in neonatal rats.Neuropharmacology 31, no. 2 (February 1992): 143–48. https://doi.org/10.1016/0028-3908(92)90024-j.
Ignar, D. M., et al. “Chronic administration of U50,488H fails to produce hypothalamo-pituitary-adrenal axis tolerance in neonatal rats.Neuropharmacology, vol. 31, no. 2, Feb. 1992, pp. 143–48. Pubmed, doi:10.1016/0028-3908(92)90024-j.
Journal cover image

Published In

Neuropharmacology

DOI

ISSN

0028-3908

Publication Date

February 1992

Volume

31

Issue

2

Start / End Page

143 / 148

Location

England

Related Subject Headings

  • Rats, Inbred Strains
  • Rats
  • Quipazine
  • Pyrrolidines
  • Pituitary-Adrenal System
  • Physostigmine
  • Neurology & Neurosurgery
  • Morphine
  • Hypothalamo-Hypophyseal System
  • Drug Tolerance