Neurochemical studies on central dopamine neurons--regional characterization of dopamine turnover

Abstract

A simple and rapid dissection procedure was adopted to sample representative areas of the main meso-telencephalic 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 (NA) were determined by liquid chromatography with electrochemical detection. Selective NA denervation with the neurotoxin DSP4 did not significantly change the DA levels in any of the regions studied, showing that the main part of the DA analysed 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 approximately equal to 20 min), indicating a very rapid DA turnover in this region. DA disappearance was clearly slower in striatum (t1/2 approximately equal to 45 min) and the slowest rates were found in the olfactory tubercle and the nucleus accumbens (t1/2 approximately equal to 1.5-2 h). The DA disappearance (t1/2 approximately equal to 45 min) pattern in the dendritic area (substantia nigra, pars reticulata) suggested an axon-terminal like behaviour 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 approximately equal to 1-2 h), while very slow in the A9 and A10 regions (t1/2 approximately equal to 3-5 h).