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, Volume 38, Issue 3–4, pp C248–C250 | Cite as

Histaminergic (H1) modulation of antinociception in morphinetolerant mice

  • S. M. Owen
  • G. Sturman
  • P. Freeman
Histamine and the Nervous System
  • 17 Downloads

Abstract

This study compares the actions of diphenhydramine (a centrally penetrating histamine H1-antagonist) and acrivastine (a peripherally acting H1-antagonist) in morphine-tolerant and morphine-naïve mice. Mice receivei morphine twice daily for 5–7 days to induce tolerance. Once tolerant, the mice again received morphine, this time after pre-treatment with diphenhydramine (30 mg/kg s.c.) or acrivastine (10 mg/kg s.c. or 5 μg intracerebroventricularly-i.c.v.). Diphenhydramine (s.c.) and acrivastine (i.c.v.) increased the action of morphine in the hot-plate test at 49±1°C. However, acrivastine (s.c.) had no effect. In morphine-naïve mice, diphenhydramine increased the antinociceptive action of morphine (5 mg/kg) as did acrivastine when given intracerebroventricularly but not subcutaneously. Therefore, H1-antagonists potentiate the antinociceptive action of morphine in both morphine-tolerant and morphine-naïve mice via a central, rather than peripheral, action.

Keywords

Morphine Histamine Diphenhydramine Antinociceptive Action Acrivastine 

References

  1. [1]
    K. E. Barke and L. B. Hough,Morphine-induced increases of extracellular histamine levels in the periaqueductal grey in vivo: a microdialysis study. Brain Res.572, 146–153 (1992).PubMedGoogle Scholar
  2. [2]
    P. Freeman and G. Sturman,Potentiation of morphineinduced antinociception in mice by centrally- but not peripherally-acting histamine H 1 antagonists. Br. J. Pharmacol.97, 486P (1989).Google Scholar
  3. [3]
    P. Freeman, G. Sturman and M.-F. Tang,Further investigation of the effects of histmaine H 1 antagonists on nociception in the mouse. Br. J. Pharmacol.98, 933P (1989).Google Scholar
  4. [4]
    T.J. Haley and W.G. McCormick,Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br. J. Pharmacol.12, 12–15 (1957).PubMedGoogle Scholar
  5. [5]
    A. F. Cohen, M. Hamilton, R. Philipson and A. W. Peck,The acute effects of activastine, (BW825C), a new antihistamine, compared with triprolidine on measures of central nervous system performance and subjective effects. Clin. Pharmacol. Ther.38, 381–386 (1985).PubMedGoogle Scholar
  6. [6]
    S. M. Owen, G. Sturman and P. Freeman,Modulation of antinociception in mice by histamine H 3-receptor ligands. Br. J. Pharmacol.106, 139P (1992).Google Scholar

Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • S. M. Owen
    • 1
  • G. Sturman
    • 1
  • P. Freeman
    • 1
  1. 1.Department of Life SciencesUniversity of East LondonLondon

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