DIFFERENCES IN THE ANTINOCICEPTIVE EFFECTS OF ALPHA-2-ADRENOCEPTOR AGONISTS IN 2 SUBSTRAINS OF SPRAGUE-DAWLEY RATS

In this study, we examined whether Sprague-Dawley rats obtained from t wo different vendors, Harlan and Sasco, differ with respect to the typ es of alpha-2 adrenoceptors in the spinal cord that mediate antinocice ption. This hypothesis was tested using two alpha-2 adrenoceptor agoni sts, dexmedetomidine and ST-91, which are relatively selective for alp ha-2A and alpha-2B adrenoceptors, respectively, and two different meas ures of nociception, the tail-flick and the 55 degrees C hot-plate tes t. Dexmedetomidine and ST-91 each increased tail-flick latency to a si milar extent in both Harlan and Sasco rats, although dexmedetomidine w as more efficacious than ST-91 in each substrain. However, the efficac y of these agonists was markedly different in Harlan and Sasco rats wh en 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 Sas co rats. Dexmedetomidine was a very weak partial agonist in Harlan rat s 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 a drenoceptors, with a minimal contribution by alpha-2A adrenoceptors in the Harlan rat and (3) hot-plate responses are not appreciably affect ed by either alpha-2a or alpha-2B adrenoceptors in the Sasco rat. Thes e 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 dependen t on the receptor selectivity of the agonist used, cutaneous tissue st imulated to elicit nociceptive responses and substrain of rat.