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OtherANALGESIA AND DRUGS OF ABUSE

Differences in the Antinociceptive Effects ofAlpha-2 Adrenoceptor Agonists in Two Substrains of Sprague-Dawley Rats

Brent A. Graham, Donna L. Hammond and Herbert K. Proudfit
Journal of Pharmacology and Experimental Therapeutics November 1997, 283 (2) 511-519;
Brent A. Graham
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Donna L. Hammond
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Herbert K. Proudfit
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Abstract

In this study, we examined whether Sprague-Dawley rats obtained from two different vendors, Harlan and Sasco, differ with respect to the types of alpha-2 adrenoceptors in the spinal cord that mediate antinociception. This hypothesis was tested using twoalpha-2 adrenoceptor agonists, dexmedetomidine and ST-91, which are relatively selective for alpha-2A andalpha-2B adrenoceptors, respectively, and two different measures of nociception, the tail-flick and the 55°C hot-plate test. Dexmedetomidine and ST-91 each increased tail-flick latency to a similar extent in both Harlan and Sasco rats, although dexmedetomidine was more efficacious than ST-91 in each substrain. However, the efficacy of these agonists was markedly different in Harlan and Sasco rats when the hot-plate test was used. For example, ST-91 was a full agonist in the hot-plate test in Harlan rats but a weak partial agonist in Sasco rats. Dexmedetomidine was a very weak partial agonist in Harlan rats and ineffective in the hot-plate test in Sasco rats. These findings suggest that (1) both spinal alpha-2A andalpha-2B receptors modulate nociceptive responses in the tail-flick test in both Harlan and Sasco rats; (2) hot-plate responses are mediated predominantly by alpha-2B adrenoceptors, with a minimal contribution by alpha-2A adrenoceptors in the Harlan rat and (3) hot-plate responses are not appreciably affected by either alpha-2A or alpha-2B adrenoceptors in the Sasco rat. These findings confirm previous reports that intrathecal administration of alpha-2 adrenoceptor agonists produces thermal antinociception in the rat. However, the magnitude of the antinociceptive effect is dependent on the receptor selectivity of the agonist used, cutaneous tissue stimulated to elicit nociceptive responses and substrain of rat.

Footnotes

  • Send reprint requests to: Brent A. Graham, M.D., Department of Anesthesia and Critical Care, University of Chicago, 5841 S. Maryland Avenue, M/C 4028, Chicago, IL 60637. E-mail:bagraham{at}midway.uchicago.edu

  • ↵1 This work was supported in part by United States Public Health Service Grant DA03980 (H.K.P.) and a Research Starter Grant from the Foundation for Anesthesia Education and Research and Hoeschst Marion Roussel (B.A.G.).

  • Abbreviations:
    i.t.
    intrathecal
    CL
    confidence limit
    HPL
    hot-plate latency
    ST-91
    2-(2,6-diethylphenylamino)-2-imidazoline
    TFL
    tail-flick latency
    • Received November 11, 1996.
    • Accepted July 15, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 283, Issue 2
1 Nov 1997
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OtherANALGESIA AND DRUGS OF ABUSE

Differences in the Antinociceptive Effects ofAlpha-2 Adrenoceptor Agonists in Two Substrains of Sprague-Dawley Rats

Brent A. Graham, Donna L. Hammond and Herbert K. Proudfit
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 511-519;

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OtherANALGESIA AND DRUGS OF ABUSE

Differences in the Antinociceptive Effects ofAlpha-2 Adrenoceptor Agonists in Two Substrains of Sprague-Dawley Rats

Brent A. Graham, Donna L. Hammond and Herbert K. Proudfit
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 511-519;
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