Effects of acute and short-term administration of tryptophan plus ethanol on noradrenaline and serotonin metabolites in the locus coeruleus.
The effects of acute and short-term administration of tryptophan or tryptophan plus ethanol on serotonin [5-hydroxytryptamine (5-HT)] and two of its metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTPL), in the locus coeruleus were investigated in rats by using the microdialysis method. In addition, the acute effects of these drugs on noradrenaline and its metabolite 4-hydroxy-3-methoxymandelic acid (HMMA) were addressed. A single co-administration of tryptophan (50 mg/kg, i.p.) and ethanol (1.25 g/kg, i.p.) did not change the concentrations of either noradrenaline or its metabolite in the locus coeruleus. In contrast, administration of tryptophan (50 mg/kg, i.p.) for three consecutive days caused an increase in the concentration of 5-HIAA, but not that of 5-HT, in the locus coeruleus. Combined administration of tryptophan plus ethanol for 3 days resulted in marked increases in 5-HIAA concentrations in the locus coeruleus, but not in 5-HTPL concentrations. However, administration of ethanol (1.25 g/kg) for 3 days had no effect on the concentrations of 5-HT and its metabolites. The increased 5-HIAA concentration that resulted with combined tryptophan plus ethanol administration was remarkably suppressed by disulfiram. Moreover, in comparison with tryptophan-treated rats, the behavioral sign of teeth-chattering was significantly detected in tryptophan plus ethanol-treated rats, but the enhancement of behavioral signs with combined treatment was markedly suppressed by disulfiram. Results of the current study seem to indicate that the stimulation of 5-HT metabolism in locus coeruleus serotonergic neurons by tryptophan was strengthened by the simultaneous administration of ethanol in short-term experiments, and that the increased 5-HIAA concentrations in the locus coeruleus are responsible for behavioral activation.
Hayashi
Masahiro
M
Department of Clinical Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan.
Bandoh
Tsutomu
T
Ushizawa
Daiki
D
Takada
Shinya
S
Hoshi
Katsuji
K
D000818:Animals; D004334:Drug Administration Schedule; D004338:Drug Combinations; D000431:Ethanol / Q000008:administration & dosage*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000008:administration & dosage*
D004338:Drug Combinations; D012701:Serotonin; D000431:Ethanol; D014364:Tryptophan; D009638:Norepinephrine