ABSTRACT

In the present study, we have investigated the effect of acute stress and repeated stress on serotonin (5-HT) receptor function in rats. We also investigated the effect of repeated treatment with lithium, electroconvulsive shock (ECS), and nimodipine, which is useful for treating patients suffering from mood disorders, on 5-HT-2A receptor function in rats with repeated dexamethasone treatment.

Acute treatment with lipopolysaccharide (LPS), interleukin (IL)-lβ, and interferon (IFN)-α attenuated wet dog shaking behavior (WDS) induced by (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), a 5-HT-2A receptor agonist.

Repeated injection for 14 days resulted in the increase in the density of 5-HT-2A receptor and DOI-produced WDS. Repeated treatment with dexamethasone (1 mg/kg/day for 14 days) increased the density of 5-HT-2A receptor, but not 5-HT-1A and α1-adrenergic receptors in the frontal cortex. DOI-elicited WDS in rats was significantly enhanced after repeated treatment with dexamethasone. Repeated treatment with lithium, ECS and nimodipine attenuated DOI-induced WDS enhanced by repeated treatment with dexamethasone.

Next, we investigated 5-HT-2A receptor and the receptor-mediated behavior of Noda epileptic rats (NERs), a newly developed epileptic rat strain. We found that some of NERs showed tonic-clonic seizures after subcutaneous injection of DOI. NERs can serve as a new and useful animal model in bipolar mood disorder research as well as epilepsy research. It is useful to investigate 5-HT-2A receptor function for understanding the pathophysiology of the disorders and for developing new treatment strategy of mood disorders.