On the significance of monoamines and their metabolites in the cerebrospinal fluid of the sheep

Abstract

Assays capable of concurrently measuring small quantities of noradrenaline, dopamine, serotonin, and several of their metabolites in cerebrospinal fluid (c.s.f.) were developed by the use of high performance liquid chromatography with electrochemical detection. For comparison, cortical subarachnoid, ventricular, cisternal and lumbar c.s.f. were obtained by puncture under barbiturate anaesthesia in sheep. Basal concentrations related to the adrenergic system, including methoxyhydroxyphenylglycol (MHPG), were similar in ventricular, cisternal and lumbar c.s.f., and those of the serotoninergic metabolites, 5-hydroxyindole-3-acetylacetic acid (5-HIAA), were similar in ventricular and cisternal c.s.f. High concentrations of the dopamine metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found only in ventricular c.s.f. Monoamine metabolites in ventricular c.s.f. under basal conditions and after various experimental manipulations were then determined over periods of 3 months in two different breeds of sheep fitted chronically with cannulae in lateral ventricles. A dose-related accumulation of all the acidic monoamine metabolites was recorded during treatment with probenecid. The increase in 5-HIAA was linear after administration of increased doses of tryptophan and 5-hydroxytryptophan. The concentrations of dopamine, DOPAC and HVA in the ventricular c.s.f. reflected the response of the dopaminergic system to agents capable of crossing the blood-brain barrier. It is concluded that cerebral metabolism in conscious sheep could be indirectly approached by recording the concentration of end-products of dopamine metabolism in ventricular cerebrospinal fluid, obtained under conditions of minimal stress.