Effect of acute and chronic administration of dehydroepiandrosterone on(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced wet dog shaking behavior in rats

It has been reported that dehydroepiandrosterone (DHEA) or dehydroepiandros terone sulfate (DHEA-S) is associated with affective disorders and that pat hology of affective disorders are related with dysfunction of serotonin(S-H T)-2A receptor-mediated responses. In this study, we investigated the effec t of DHEA on (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI), 5-H T-2A receptor agonist, -induced wet dog shaking behavior (WDS) in rats. Acute treatment with DHEA inhibited the DOI-induced WDSs dose dependently. This inhibition was recovered by opioid receptor antagonist, naltrexone. 5- HT-2A receptor-mediated WDSs were desensitized after chronic treatment with DOI, however chronic treatment with DHEA had no effect on this desensitiza tion. Chronic treatment with DHEA had no facilitating effect of chronic dexametha sone treatment on DOI-induced WDSs. These findings may lead the possibility that DHEA has the inhibitory effect of 5-HT-2A mediated signaling pathway via non-genomic action.