ABSTRACT
K. HOSHI *, M. HAYASHI and T. BANDOH Department of Clinical Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan
Abstract-The present review will concentrate on a discussion of recent investigations that demonstrated whether the levels of 5-hydroxytryptamine (serotonin; 5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in the locus coeruleus are influenced by tryptophan alone or simultaneous administration of tryptophan and ethanol. The impetus for this line of investigation derives from a report that mice treated with tryptophol plus alcohol increased brain tryptophol level and became highly susceptible to convulsions. A deficiency in 5-HT synthesis and metabolism (turnover) has been implicated in several neuropsychiatric disorders, including depression, obsessive-compulsive disorder, bulimia nervosa, late luteal phase dysphoric syndrome, alcoholism, impulsive violence and aggression. Emphasis will be placed on demonstration of a rodent model in which the tryptophan administration induces the increased 5-HIAA level through the activation of serotonergic neuronal system. The use of in vivo microdialysis techniques clearly identifies, in this model, that acutelyor consecutively-treated tryptophan plus ethanol results in focal increases in extracellular levels of 5-HIAA within the locus coeruleus. This study provides evidence to indicate that the 5-HIAA level in the locus coeruleus after tryptophan alone or tryptophan plus ethanol is indicative of changes in the activity of serotonergic neurotransmission in locus coeruleus neurons and the participation of 5-HIAA as a general phenomenon in behavioral activation.
