Dopamine Metabolites in Rat Cisternal Cerebrospinal Fluid: Major Contribution from Extrastriatal Dopamine Neurones

Abstract

The interpretation of central 3,4-dihydroxyphenylethylamine (dopamine, DA) metabolism, as indicated by determinations in rat cisternal CSF, was investigated using intrastriatal injection of the DA neurotoxin 6-hydroxydopamine (6-OHDA) and intraperitoneal injection of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). DA turnover was subsequently determined by measurement of the rate of accumulation of total 3,4-dihydroxyphenylacetic acid and homovanillic acid (DOPAC + HVA) in the CSF after probenecid was given. Two days later the rats were killed, and metabolism of DA and 5-hydroxytryptamine (5-HT) was investigated by determining levels of the amines and their metabolites in brain regions. Although 6-OHDA greatly decreased striatal DA metabolism, this was not paralleled by DA turnover as indicated by CSF, as this fell only moderately and approximately in parallel with results for the brain as a whole. 5-HT metabolism was essentially unaltered. DSP4 considerably depleted noradrenaline and caused smaller decreases of 5-HT metabolism in some regions. However, DA metabolism was not significantly affected, either in brain or CSF, which suggests that noradrenaline neurones make only a small contribution to central DA metabolism. Results as a whole suggest that DOPAC and HVA concentrations in rat cisternal CSF reflect whole brain DA metabolism and derive predominantly from DA neurones in extrastriatal regions of the brain.