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Preservation of dopamine release in the denervated striatum
1Pharmaceuticals Division, Ciba-Geigy Corporation, Summit, NJ 07901.
Abstract:
Dopamine metabolism and release were determined in the striata of rats sustaining varying damage to the nigrostriatal dopamine (DA) projection. DA metabolism, inferred from concentrations of dihydroxy-phenylacetic acid (DOPAC) or homovanillic acid (HVA), decreased with DA denervation of more than 20%. Dopamine release, inferred from the concentration of 3-methoxytyramine (3-MT), did not decrease unless the denervation was at least 80%. The amount of 3-MT per surviving neuron exceeded that for DOPAC over most of the denervation range. Thus, striatal DA release is preserved at normal levels with the survival of only 20% of the striatal DA innervation. Decreases in DA release, rather than decreases in DA metabolism or the density of dopamine innervation, coincide with the appearance of behavioral impairments.