Effect of RU 24969 on 5-HT metabolism in the medullary dorsal horn as studied by in vivo voltammetry.

The effect of i.p. administration of the preferential 5-HT1B agonist 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969) (10 mg/kg) has been investigated by in vivo 5-hydroxyindole electrochemical (peak 3) detection in the medullary dorsal horn (MDH) of acute anesthetized and unanesthetized freely moving rats. RU 24969 induced a significant decrease in peak 3 in the MDH of anesthetized rats. In freely moving animals, RU 24969 induced a biphasic effect. Thus, after the injection the curve remained above that of the saline group and returned to control levels up to 60 min. Subsequently the curve decayed to below the control values and rapidly plateaued for up to 180 min. The initial increase and the decrease thereafter were both statistically significant vs. saline. With reference to similar in vivo studies demonstrating the responsiveness of ascending serotonergic systems to RU 24969, it is concluded that the 5-HT metabolism in the serotonergic NMR-dorsal horn system is affected by this 5-HT1B agonist. However, the biphasic effect reported here in unanesthetized animals suggests that RU 24969 could act by two different ways on 5-HT metabolism and indicates that there could be a primary interaction of RU 24969 on the 5-HT uptake system (inhibition) which could, at first, prevail over the interaction with terminal autoreceptors.