Inhibition of K(+)-evoked release of rat striatal 5-hydroxytryptamine by an atypical antidepressant: trazodone.
Using microdialysis, extracellular concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the striatum of rats. In rats given trazodone, m-chlorophenylpiperazine dihydrochloride, or imipramine, the concentrations of 5-HT were unchanged. 5-HIAA in trazodone- or imipramine-treated rats, however, was respectively, decreased to 80 or 65% of preinjections levels. When the potassium concentration (K(+)) was increased up to 150 mmol/l in the perfusate, the concentrations of 5-HT increased to about ten times the basal levels in the rats given saline. In rats treated with trazodone, K(+)-evoked elevations of 5-HT were less than five times the basal level. Multiple trazodone administrations prolonged the duration of inhibition of 5-HT release. In rats treated with other drugs, the K(+)-evoked 5-HT release was not affected. These observations suggest that trazodone itself might reduce 5-HT neural transmission.
Hatsuda
S
S
Department of Neuropsychiatry, Aichi Medical College, Nagakute, Japan.
Sugita
S
S
Suzuki
S
S
Matsubara
M
M
Ozaki
N
N
Kayukawa
Y
Y
Ohara
M
M
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014196:Trazodone / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D007099:Imipramine; D011188:Potassium; D014196:Trazodone