NEUROCHEMICAL STUDIES ON CENTRAL DOPAMINE NEURONS - REGIONAL CHARACTERIZATION OF DOPAMINE TURNOVER

  • 1 January 1984
    • journal article
    • research article
    • Vol. 62  (3) , 198-209
Abstract
A simple and rapid dissection procedure was adopted to sample representative areas of the main mesotelencephalic dopaminergic (DA) neuron systems (nigrostriatal and meso-limbic-cortical) in the rat CNS. The object was to explore nerve terminal fields, cell body groups and dendrites, and to investigate the DA utilization rates in these regions. DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as well as noradrenaline [Norepinephrine] (NA) were determined by liquid chromatogrpahy with electrochemical detection. Selective NA denervation with the neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] did not significantly change the DA levels in any of the regions studied, showing that the main part of the DA analzyed originated from DA neurons. Administration of the tyrosine hydroxylase inhibitor .alpha.-methyl-p-tyrosine (H44/68) resulted in a time-dependent, often multi-phasic, DA and NA depletion pattern that varied between different regions. Comparison between the rate of DA decline and DOPAC/DA or HVA/DA ratios (also indices for DA utilization) in the various regions showed that the initial rate of DA disappearance after H44/68 appeared to be the most relevant index of DA utilization. The most rapid initial DA decline after H44/68 was found in the cortical regions (frontal, cingulate, and entorhinal) and the cell body areas A9 and A10, in particular in the cingulate cortex (t1/2 .apprxeq. 20 min) indicating a very rapid DA turnover in this region. DA disappearance was clearly slower in striatum (t1/2 .apprxeq. 45 min) and the slowest rates were found in the olfactory tubercle and the nucleus accumbens (t1/2 .apprxeq. 1.5-2 h). The DA disappearance (t1/2 .apprxeq. 45 min) pattern in the dendritic area (substantia nigra, pars reticulata) suggested an axon-terminal like behavior of the DA dendrites with respect to DA utilization. In general, the Da metabolite/DA ratios obtained for the various regions agreed closely with these results. The rate of NA disappearance after H44/68 was slower than that of DA in most regions. The most rapid NA decline was found in the cortical regions (t1/2 .apprxeq. 1-2 h), while very slow in the A9 and A10 regions (t1/2 .apprxeq. 3-5 h).