Acute effect of simultaneous administration of tryptophan and ethanol on serotonin metabolites in the locus coeruleus in rats.
Using the microdialysis method, we investigated whether the levels of serotonin (5-hydroxytryptamine, 5-HT) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTPL), in the locus coeruleus are influenced by tryptophan alone or simultaneous administration of tryptophan and ethanol. Tryptophan (50 mg/kg, i.p.) led to a significant increase in the levels of 5-HIAA, but not 5-HT in the locus coeruleus. However, ethanol (1.25 g/kg) had no effect on the levels of 5-HT and its metabolites. Combined administration of tryptophan and ethanol caused very marked increases in 5-HIAA and 5-HTPL levels in the locus coeruleus. A time lag in the increased 5-HIAA levels between tryptophan alone and tryptophan plus ethanol was observed. Moreover, 5-HIAA levels in the locus coeruleus induced by tryptophan were abolished by microinjection of 5,7-dihydroxytryptamine (150 microg/4 microl) into the dorsal raphe nucleus. Judging from the present results, the serotonergic afferents to the locus coeruleus may originate for about 20-30% from cell bodies located in the dorsal raphe nucleus. Teeth-chattering was significantly detected in the tryptophan plus ethanol-treated rats when compared with the tryptophan-treated rats, but not in the saline-treated controls. These results may suggest that the increased levels of 5-HIAA and 5-HTPL in the locus coeruleus induced by tryptophan are potentiated by ethanol, and that these levels are partly responsible for behavioral activation.
Hayashi
Masahiro
M
Department of Clinical Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan.
Nakai
Tohru
T
Bandoh
Tsutomu
T
Hoshi
Katsuji
K
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006917:Hydroxytryptophol / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000008:administration & dosage / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D002492:Central Nervous System Depressants; D006917:Hydroxytryptophol; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan