Pharmacological Analysis of the Behavioural and Thermoregulatory Effects of the Putative 5-HT1 Receptor Agonist, RU 24969, in the Rat

The roles of recognition sites for central neurotransmitters in the mediation of the behavioural effects of the putative 5-hydroxytryptamine (5-HT1) receptor agonist, RU 24969 [5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole] in the rat have been examined. The drug RU 24969 was found to have high affinity for 5-HT1A and 5-HT1B recognition sites. Hyperlocomotion, induced by RU 24969, was enhanced in animals depleted of 5-HT with 5,7-dihydroxytryptamine, suggesting an involvement of 5-HT receptors in the mediation of this behaviour. However, results of experiments with 5-HT receptor antagonists argued against the receptors being of either the 5-HT1 or 5-HT2 type. Despite the negligible affinity of RU 24969 for catecholamine receptors, hyperlocomotion induced by RU 24969 was clearly dependent on intact catecholamine systems. When hyperlocomotion was blocked by treatment with reserpine, reciprocal forepaw-treading and a flat body posture, behavioural responses which are consistent with activation of the putative 5-HT1A receptor, became evident. When animals were restrained from moving, RU 24969 dose-dependently reduced body temperature, an effect that may also be associated with activation of the 5-HT1A recognition site. Thus, although the mechanism by which RU 24969 induces hyperlocomotion is not yet established, the agonist nevertheless can induce functional responses consistent with its high affinity for the 5-HT1A recognition site.