Abstract
The selective 5-HT 3 receptor agonist 2-methyl-serotonin (2-Me-5-HT) mimicked the antinociceptive activity of 5-HT when intrathecally administered to rats. Two hundred μg (i.t.) doses of these agonists produced similar increases in tail flick latency. However, equal doses of 2-Me-5-HT and 5-HT doubled and tripled, respectively, the mean response latency as measured by the hot plate test. The potent and selective 5-HT 3 receptor antagonists ICS 205-930 (3-tropanyl-indole-3-car☐ylate) and MDL 72222 (3-tropanyl-3, 5-dichlorobenzoate) antagonized the antinociceptive effects of both 5-HT and 2-Me-5-HT. However, there were differences in the efficacy of these antagonists. Thus, intrathecal pretreatment with ICS 205-930 (0.05 μg) or MDL 72222 (0.1 μg) blocked the antinociceptive effects of 5-HT (200 μg, i.t.) as measured by the tail flick test, however, higher doses (0.1 and 1.0 μg, respectively) were required in the hot plate test. Pretreatment with ICS 205-930 (0.1 μg) or MDL 72222 (0.1 μg) blocked the effects of 2-Me-5-HT (200 μg, i.t.) in both analgesiometric tests. It is concluded that 5-HT 3 receptors are intimately involved in the modulation of spinal nociceptive responses.
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