Formation and Metabolism of Dopamine in Nine Areas of the Rat Brain: Modifications by Haloperidol

Abstract

The rate of removal of 3,4-dihydroxyphenylacetic acid (DOPAC) in 9 rat brain areas (striatum, nucleus accumbens, tuberculum olfactorium, hypothalamus, lateral hippocampus, occipatal cortex, brain stem, cerebellum and retina) was calculated from its exponential decline after monoamine oxidase inhibition by pargyline. The experiments were carried out with rats pretreated with either saline or haloperidol. The efficiency with which DOPAC was removed from the brain (expressed by the fractional rate constant k) varied considerably throughout the brain. Haloperidol dramatically decreased the k values, and in addition these effects differed widely in the various brain areas. Similarly to DOPAC, haloperidol had a pronounced retarding effect on the efflux of homovanillic acid (HVA)from the brain. These findings strongly suggest that great care should be taken when drug-induced alterations in DOPAC and HVA concentrations are interpreted as changes in dopaminergic activity. The dopamine (DA) concentrations were measured in the same experiments, but it appeared that the pargyline-induced rise in DA was of limited use for the estimation of the synthesis rate of the amine. The rate of catecholamine synthesis in the 9 brain areas was calculated from the rise of dopa during decarboxylase inhibition. In saline- as well as in haloperidol-pretreated rats the total catecholamine synthesis rate in the typical dopaminergic areas (striatum, nucleus accumbens and tuberculum olfactorium) was of the same order or magnitude as the DOPAC rate of removal. This confirms that DOPAC formation is quantitatively the main route of degradation in these brain areas. If it is assumed that DOPAC is also the main metabolite in other brain areas, it is possible to calculate from the DOPA accumulation rate and the DOPAC removal rate which part of the catecholamine synthesis is destined for formation of noradrenaline and which part is used for DA and subsequently metabolized to DOPAC. The ratios between the rate of removal of DOPAC and the DA content for the 9 brain areas was determined. DA is metabolized much faster in the lateral hippocampus and cerebellum than in the other brain areas studied.