Hypothermia and the 5-HT syndrome induced by CGS 12066B independently of 5-HT1B receptor activation

The effects of CGS 12066B (3-14 mg/kg), a putative 5-HT1B agonist, on 5-HT behavioral syndrome, motor activity and body temperature, were investigated in rats. The animal were well adapted to the experimental conditions before testing, and data sampling started at the same hour for each rat. The highest dose of CGS 12066B clearly reduced body temperature and induced flat body posture and hindlimb abduction. No significant change was seen in motor activity. The CGS 12066B-induced changes were not antagonized by 5-HT1B receptor antagonists, or antagonists at other 5-HT receptors. In fact, the 5-HT1A antagonist NAN-190 and especially the non-selective 5-HT antagonist methiothepin, with definite 5-HT1B receptor blocking properties, both potentiated the decrease in body temperature. The findings suggest that the behavioral and body temperature effects of CGS 12066B are not easily explained by 5-HT1B receptor stimulation, but may be mediated by activation of non-serotonergic mechanisms. Similar conclusions in studies with other 5-HT1B agonists suggest a common problem with such drugs.