Aromatic l -amino acid decarboxylase immunoreactive cells in the rat striatum: a possible site for the conversion of exogenous l -DOPA to dopamine

Aromatic l -amino acid decarboxylase immunoreactive cells in the rat striatum: a possible site... The efficacy of l -dihydroxyphenylalanine ( l -DOPA) in ameliorating the symptoms of Parkinson's disease (PD) is attributed to its conversion to dopamine (DA) by the enzyme aromatic l -amino-acid decarboxylase (AADC) in the striatum. Although the site of this conversion in the DA-denervated striatum has yet to be identified, it has been proposed that l -DOPA could be converted to DA at non-dopaminergic sites containing AADC. In the present study, we used immunocytochemical techniques to examine the localization of AADC and DA in the striatum of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopaminergic projection. In the DA-denervated striatum, we observed AADC-immunoreactive (-IR) cells with morphological characteristics similar to a class of small aspiny interneuron. Although usually obscured by a dense plexus of AADC-IR fibers, these cells could also occasionally be detected in the intact striatum. Acute administration of L-DOPA to DA-denervated animals elicited contralateral rotational behavior as well as a pronounced c- fos protein immunoreactivity in the striatum ipsilateral to the lesion. Following acute administration of l -DOPA, but not after acute saline, DA-IR cells were detected in the denervated striatum. These DA-IR cells are similar in morphology and were found in the same location as the AADC-IR cells. These results strongly suggest the existence of a class of AADC-containing striatal cells that can form DA from exogenous l -DOPA in the rat. In the DA deafferented striatum, DA produced by these cells from exogenous l -DOPA could be released to exert physiological effects on DA receptive tissue. It is possible that similar cells could contribute to the efficacy of l -DOPA in the treatment of Parkinson's disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Aromatic l -amino acid decarboxylase immunoreactive cells in the rat striatum: a possible site for the conversion of exogenous l -DOPA to dopamine

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Abstract

The efficacy of l -dihydroxyphenylalanine ( l -DOPA) in ameliorating the symptoms of Parkinson's disease (PD) is attributed to its conversion to dopamine (DA) by the enzyme aromatic l -amino-acid decarboxylase (AADC) in the striatum. Although the site of this conversion in the DA-denervated striatum has yet to be identified, it has been proposed that l -DOPA could be converted to DA at non-dopaminergic sites containing AADC. In the present study, we used immunocytochemical techniques to examine the localization of AADC and DA in the striatum of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopaminergic projection. In the DA-denervated striatum, we observed AADC-immunoreactive (-IR) cells with morphological characteristics similar to a class of small aspiny interneuron. Although usually obscured by a dense plexus of AADC-IR fibers, these cells could also occasionally be detected in the intact striatum. Acute administration of L-DOPA to DA-denervated animals elicited contralateral rotational behavior as well as a pronounced c- fos protein immunoreactivity in the striatum ipsilateral to the lesion. Following acute administration of l -DOPA, but not after acute saline, DA-IR cells were detected in the denervated striatum. These DA-IR cells are similar in morphology and were found in the same location as the AADC-IR cells. These results strongly suggest the existence of a class of AADC-containing striatal cells that can form DA from exogenous l -DOPA in the rat. In the DA deafferented striatum, DA produced by these cells from exogenous l -DOPA could be released to exert physiological effects on DA receptive tissue. It is possible that similar cells could contribute to the efficacy of l -DOPA in the treatment of Parkinson's disease.

Journal

Brain ResearchElsevier

Published: Dec 15, 1995

References

  • Effect of L-DOPA loading on 5-HTP decarboxylation in rat brain areas
    Trouvin, J.H.; Maubrey, M.C.; Raynal, H.; Jacquot, C.

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