Extracellular serotonin, dopamine and glutamate levels are elevated in the hypothalamus in a serotonin syndrome animal model induced by tranylcypromine and fluoxetine.
Serotonin (5-HT) syndrome is a potentially fatal condition associated with various combinations of serotonergic drugs. The present study was undertaken to demonstrate that nervous systems other than the 5-HT system also participate in the pathophysiology of 5-HT syndrome. Concentrations of 5-HT, dopamine (DA) and glutamate in the hypothalamus were measured in two different 5-HT syndrome animal models using a microdialysis technique. The first model was induced by tranylcypromine, a nonselective monoamine oxidase (MAO) inhibitor (3.5 mg/kg) and fluoxetine, a selective serotonin reuptake inhibitor (SSRI) (10 mg/kg). The second model was induced by clorgyline, an MAO-A inhibitor (1.2 mg/kg) and 5-hydroxy-L-tryptophan, a precursor of 5-HT (5-HTP) (80 mg/kg). In the first model, the levels of 5-HT and DA increased by 40-fold and 44-fold, respectively, compared with the preadministration levels. In the second model, the concentrations of 5-HT increased by up to 140-fold, whereas DA levels increased by only 10-fold, of the preadministration levels. Although the level of glutamate in the second model barely changed, a delayed increase in the glutamate level was observed in the first 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 in which the DA concentration markedly increases.
Department of Psychiatry, Jichi Medical School, Minamikawachi-Machi, Kawachi-Gun, Tochigi-Ken, 329-0498, Japan.
Katsutoshi
K
Shioda
Koichi
K
Nisijima
Tatsuki
T
Yoshino
Satoshi
S
Kato
D000818:Animals; D000928:Antidepressive Agents / Q000633:toxicity*; D015306:Biogenic Monoamines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D005473:Fluoxetine / Q000633:toxicity*; D018698:Glutamic Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D020230:Serotonin Syndrome / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*; D014191:Tranylcypromine / Q000633:toxicity*
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D004298:Dopamine; D005473:Fluoxetine; D018698:Glutamic Acid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014191:Tranylcypromine