HYPOTHERMIA AND THE 5-HT SYNDROME INDUCED BY CGS 12066B INDEPENDENTLYOF 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 in vestigated in rats. The animal were well adapted to the experimental c onditions before testing, and data sampling started at the same hour f or each rat. The highest dose of CGS 12066B clearly reduced body tempe rature and induced flat body posture and hindlimb abduction. No signif icant change was seen in motor activity. The CGS 12066B-induced change s were not antagonized by 5-HT1B receptor antagonists, or antagonists at other 5-HT receptors. In fact, the 5-HT1A antagonist NAN-190 and es pecially 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 t emperature effects of CGS 12066B are not easily explained by 5-HT1B re ceptor stimulation, but may be mediated by activation of non-serotoner gic mechanisms. Similar conclusions in studies with other 5-HT1B agoni sts suggest a common problem with such drugs.