title: Acyclovir inhibits rat liver tryptophan-2,3-dioxygenase and induces a concomitant rise in brain serotonin and 5-hydroxyindole acetic acid levels.
abstract: Viral diseases of the brain may induce changes in neurotransmitter synthesis and metabolism. In experimental herpes simplex encephalitis, brain serotonin is reduced, whilst it's major metabolite, 5-hydroxyindole acetic acid and turnover is increased. It is well established that reduced levels of brain monoamines, serotonin and norepinephrine may contribute to the symptoms of clinical depression, which raises the possibility that this condition is prevalent in herpes simplex encephalitis. An inverse relationship exists between liver tryptophan-2,3-dioxygenase activity and brain serotonin levels and there is an interdependency between serotonin and norepinephrine levels. The aim of this study is to determine the effect of acyclovir, an antiviral used in the treatment of herpes simplex encephalitis, on rat liver tryptophan-2,3-dioxygenase activity in vitro and in vivo as well as on rat forebrain serotonin, 5-hydroxyindole acetic acid and norepinephrine levels. The results show that acyclovir inhibits tryptophan-2,3-dioxygenase activity in vitro and in vivo, with a concomitant rise in serotonin and 5-hydroxyindole acetic acid levels. However, acyclovir reduces the turnover of serotonin to 5-hydroxyindole acetic acid, without any effect on norepinephrine levels. It appears that acyclovir may have the potential to reduce the clinical symptoms of depression in herpes simplex encephalitis. However, a greater turnover of serotonin to 5-hydroxyindole acetic acid could possibly be masked by conversion of serotonin to 5-hydroxytryptophol, which needs to be investigated further.
authors.affiliation: Division of Pharmacology, Faculty of Pharmacy, Rhodes University, P.O. Box 94, Grahamstown, 6140 Eastern Cape, South Africa.
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Müller
authors.forename: Santy
authors.initials: S
authors.lastname: Daya
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D004791:Enzyme Inhibitors; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D006917:Hydroxytryptophol / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006917:Hydroxytryptophol; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014366:Tryptophan Oxygenase; D000212:Acyclovir; D009638:Norepinephrine