Document Detail

Differences in the antinociceptive effects of alpha-2 adrenoceptor agonists in two substrains of Sprague-Dawley rats.
MedLine Citation:
PMID:  9353364     Owner:  NLM     Status:  MEDLINE    
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 two alpha-2 adrenoceptor agonists, dexmedetomidine and ST-91, which are relatively selective for alpha-2A and alpha-2B adrenoceptors, respectively, and two different measures of nociception, the tail-flick and the 55 degrees 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 and alpha-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.
B A Graham; D L Hammond; H K Proudfit
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  283     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-12-08     Completed Date:  1997-12-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  511-9     Citation Subset:  IM    
Department of Anesthesia and Critical Care, University of Illinois at Chicago, Chicago, Illinois 60637, USA.
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MeSH Terms
Adrenergic alpha-Agonists / pharmacology*
Analgesics, Non-Narcotic / pharmacology*
Clonidine / analogs & derivatives,  pharmacology
Dose-Response Relationship, Drug
Imidazoles / pharmacology
Injections, Spinal
Rats, Sprague-Dawley
Receptors, Adrenergic, alpha-2 / agonists*
Species Specificity
Spinal Cord / drug effects*
Grant Support
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Analgesics, Non-Narcotic; 0/Imidazoles; 0/Receptors, Adrenergic, alpha-2; 4205-90-7/Clonidine; 4751-48-8/ST 91; 86347-14-0/Medetomidine

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