|Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Serotonin (5-HT) syndrome is an uncommon but potentially life-threatening complication of antidepressants, however, its pathophysiology has never been elucidated. In the present study, we induced 5-HT syndrome in two different animal models. In the first model, 5-HT syndrome was induced by the simultaneous administration of clorgyline, a MAO-A inhibitor (1.2 mg/kg, i.p.) and 5-hydroxy-L-tryptophan, a precursor of 5-HT (5-HTP) (80 mg/kg, i.p.). In the second model, 5-HT syndrome was induced by the simultaneous administration of tranylcypromine, a nonselective MAO inhibitor (3.5 mg/kg, i.p.) and fluoxetine, a selective serotonin reuptake inhibitor (10 mg/kg, i.p.). In both models, 5-HT behavioral syndromes were observed, and the rectal temperature of the rats increased to about 40℃. In the first model, the concentrations of 5-HT and dopamine in the hypothalamus increased 140-fold and 10-fold the pre-administration levels, respectively. In the second model, the levels of 5-HT and dopamine in the hypothalamus increased 40-fold and 44-fold the pre-adminietration levels, respectively. Although the level of glutamate in the first model barely changed, a delayed increase in the glutamate level was observed in the second model. These findings suggest that not only hyperactivity of the 5-HT system but also hyperactivity of the DA system are present in 5-HT syndrome, and that the glutamatergic system is influenced in some 5-HT syndrome cases.