Studies on Increased Turnover of Brain Mono-Amines Induced by Experimental Herpes Simplex Infection



Intracerebral infection of mice with different herpes simplex virus (HSV) strains caused raised dopamine and 5-hydroxytryptamine turnover, reflected in increased brain concentrations of the acid metabolites of the amines i. e. homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA). Inhibitors of virus multiplication (actinomycin D, mitomycin C and iododeoxyuridine) and different variants of HSV were used to study whether the rise in mono-amine metabolism was an event dependent upon the direct action of the virus or viral metabolites on pathways of mono-amine synthesis. The results obtained were not compatible with such a hypothesis. The histopathological study of the distribution of the neuronal lesions indicated that the lower brain stem from which most of the monoaminergic neurons originate was hardly affected at all. The degree of severity of the neuronal lesions in relation to the HVA and 5-HIAA concentrations found in infected brains was studied for 13 different HSV variants. The more extensive and frequent the lesions, the higher were the levels of the acids encountered. It was assumed that impaired functions of postsynaptic cells or altered receptor-functions possibly affecting regulatory feed-back mechanisms could be responsible for the increased mono-amine turnover.