DIFFERENTIAL INFLUENCE OF 2 SEROTONIN 5-HT3 RECEPTOR ANTAGONISTS ON SPINAL SEROTONIN-INDUCED ANALGESIA IN RATS

We tested the antinociceptive effect of intrathecal (i.t.) administrat ion of 5-HT and the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguani de (mCPBG), in rats submitted to a mechanical noxious stimulus and the influence of the 5-HT3 receptor selective antagonists, tropisetron an d granisetron. Both 5-HT and mCPBG (0.01, 0.1, 1, 10, 20 mu g/rat) pro duced a significant dose-dependent antinociception. The lowest active doses were 0.1 and 1 mu g for 5-HT and mCPBG, respectively. The effect , observed with 20 mu g, was significantly lower with mCPBG (+33 +/- 6 %) than with 5-HT (+63 +/- 7%). For 5-HT-induced antinociception, the minimal inhibitory doses were 0.001 mu g/rat for tropisetron and 10 mu g/rat for granisetron. In contrast, the same doses of the two antagon ists (from 0.1 mu g/rat) similarly inhibited the effect of mCPBG. This study provides evidence that contrary to tropisetron, doses of granis etron able to inhibit the effect of a 5-HT3 receptor agonist failed to reduce that of 5-HT. This demonstrates a heterogeneity between 5-HT3 receptor antagonists and questions the true involvement of these recep tors in spinal 5-HT-induced actinociception. (C) 1997 Elsevier Science B.V.