Differential effect of acute and chronic ethanol on dopamine metabolism in frontal cortex, caudate nucleus and substantia nigra.
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Biomedical subjects
Publications and source records attributed to F Fadda.
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The effect of tiapride on HVA and 5-HIAA levels in the CSF drawn at pneumoencephalography (PEG) was studied. Five consecutive 5 ml fractions of CSF were drawn from control and tiapride-treated subjects. In both groups, a linear increase in HVA concentrations was found between the first and subsequent fractions. On the contrary, no significant difference in 5-HIAA concentrations was found in sequential CSF samples. Tiapride increased the mean HVA concentrations and caused a steeper caudocranial gradient of this metabolite but failed to modify 5-HIAA concentrations. The results suggest that tiapride blocks dopamine (DA) receptors and increases DA synthesis.
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In this preliminary report we showed that 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine (DA), is present in the ventral tegmental area. This finding indicates that in the ventral tegmental area, which contains the cell bodies of dopaminergic neurons of the mesocortical and mesolimbic DA systems, DA may be released by a mechanism similar to that operating in the nerve endings. However, haloperidol, which increases DOPAC levels in the substantia nigra, failed to do so in the ventral tegmental area. The results support the contention that DA neurons in the ventral tegmental area have distinctive features from nigral DA neurones.
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Electric foot-shock stress (20 min) increases DOPAC content in the frontal cortex (by about 80%) and in the nucleus accumbens (by 35%) but not in the striatum. However, foot shock stress failed to modify the kinetic properties of tyrosine hydroxylase (Vmax, Km for DMPH4 cofactor) in any of the above areas. Similar results were obtained in rats in which noradrenergic terminals in the n. accumbens and in the frontal cortex had been eliminated by injection of 6-OH-dopamine into the ascending dorsal noradrenergic bundle. The results support the hypothesis that limbic and cortical DA is involved in emotional states and indicate that DA synthesis may be regulated independently from changes in the kinetics properties of tyrosine hydroxylase.
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A radioenzymatic method for simultaneous determination of dopamine and DOPAC in small brain areas is described. By using this assay, 250 pg of dopamine and 150 pg of DOPAC can be estimated. The present method has been applied to compare the effect of different psychotropic drugs on the dopamine and DOPAC levels in the caudate nucleus, substantia nigra and medial basal hypothalamus.
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