8-OH-DPAT-Induced Hypothermia in Rodents. A Specific Model of 5-HT_lA Autoreceptor Function?

Summary

8-OH-DPAT induces hypothermia in rodents. In mice, this response is selectively attenuated by various antagonists of 5-HT₁, but not 5-HT₂, receptors. Studies with 5,7-DHT or PCPA demonstrate that the 5-HT receptors involved are located on central 5-HT neurones. Although the hypothermia is probably mediated by activation of 5-HT_1A somatodendritic autoreceptors in the raphe nucleus, the response is also influenced by antagonism of dopaminergic and noradrenergic receptors. Repeated antidepressant administration attenuates 8-OHDPAT-induced hypothermia in mice, albeit at high dose in some instances. In addition, down-regulation is also observed with certain other classes of psychotropic agent. In rats, although there is reasonable evidence to show that 8-OH-DPAT decreases body temperature by activating 5-HT _1Areceptors, their synaptic location is uncertain. There have been few studies which have investigated the adaptation of these receptors in rats after prolonged administration of psychotropic drugs and those effects reported have been inconsistent. Overall, the response in mice, but not rats, provides a valuable, functional index of somatodendritic 5-HT_1A autoreceptor function and, in addition, is a useful predictive measure of potential antidepressant activity.