Biol. Pharm. Bull. 30(1) 117—120 (2007)

the brain. Several studies have indicated that the activation of the hypothalamic-pituitary-adrenal axis changes the serotonin (5-hydroxytryptamine, 5-HT) function in the brain. The 5-HT receptor subtypes, particularly 5-HT2A and 5-HT1A receptors, have been postulated to play an important role in the pathogenesis of depression. Some clinical studies have demonstrated increases in the number of 5-HT2A receptorbinding sites in the postmortem brains of both suicides and depressed subjects. Our previous studies have already reported that chronic adrenocorticotropic hormone (ACTH) treatment increases the wet-dog shake response induced by ( )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 5-HT2A receptor agonist. 6) Thus, we suggested that chronic ACTH-treated rats could induce the hyperactivity of the 5-HT2A receptor via the activation of the hypothalamicpituitary-adrenal axis. On the other hand, numerous investigations have demonstrated interactions between the brain 5-HT1A receptor function and the hypothalamic-pituitary-adrenal axis. It was reported that chronic treatment with corticosterone decreased 5-HT1A receptor binding and the levels of 5-HT1A receptor mRNA in the hippocampus. We demonstrated that hypercorticism, which raises circulating corticosterone levels, decreased the 5-HT1A receptor binding in hippocampal membranes. Thus, the enhancement of the hypothalamic-pituitary-adrenal axis produced dysfunction of the 5-HT1A receptor mechanism. Furthermore, several studies have suggested that there are functional interactions from 5-HT2A receptor function to 5HT1A receptor function. It has been reported that 8-hydroxy2-di-n-propylamino tetralin (8-OH-DPAT), 5-HT1A receptor full agonist, inhibited DOI-induced head twitch behavior in naive rats. These results supported the hypothesis that 5-HT1A receptors exert an inhibitory control over the activation of 5-HT2A receptors. Such interactions may play an important role in the mechanism of action of antidepressant drugs. As previous studies have been used for normal rats, the model of the hypothalamic-pituitary-adrenal axis activation is interesting from the viewpoint of the mechanism of interaction between 5-HT2A and 5-HT1A receptor function, or of the action of the 5-HT1A receptor agonist. In the present study, we examined the influence of 8-OHDPAT on the effect of chronic ACTH treatment increasing the DOI-induced wet-dog shakes, and also examined 8-OHDPAT-induced hypothermia and flat body posture, as an index reflective of 5-HT1A receptor function.