A. Mura et al., AROMATIC L-AMINO-ACID DECARBOXYLASE IMMUNOREACTIVE CELLS IN THE RAT STRIATUM - A POSSIBLE SITE FOR THE CONVERSION OF EXOGENOUS L-DOPA TO DOPAMINE, Brain research, 704(1), 1995, pp. 51-60
The efficacy of L-dihydroxyphenylalanine (L-DOPA) in ameliorating the
symptoms of Parkinson's disease (PD) is attributed to its conversion t
o dopamine (DA) by the enzyme aromatic L-amino-acid decarboxylase (AAD
C) in the striatum. Although the site of this conversion in the DA-den
ervated striatum has yet to be identified, it has been proposed that L
-DOPA could be converted to DA at non-dopaminergic sites containing AA
DC. In the present study, we used immunocytochemical techniques to exa
mine the localization of AADC and DA in the striatum of rats with a un
ilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopami
nergic projection. In the DA-denervated striatum, we observed AADC-imm
unoreactive (-IR) cells with morphological characteristics similar to
a class of small aspiny interneuron. Although usually obscured by a de
nse plexus of AADC-IR fibers, these cells could also occasionally be d
etected in the intact striatum. Acute administration of L-DOPA to DA-d
enervated animals elicited contralateral rotational behavior as well a
s a pronounced c-fos protein immunoreactivity in the striatum ipsilate
ral to the lesion. Following acute administration of L-DOPA, but not a
fter acute saline, DA-IR cells were detected in the denervated striatu
m. These DA-IR cells are similar in morphology and were found in the s
ame location as the AADC-IR cells. These results strongly suggest the
existence of a class of AADC-containing striatal cells that can form D
A from exogenous L-DOPA in the rat. In the DA deafferented striatum, D
A produced by these cells from exogenous L-DOPA could be released to e
xert physiological effects on DA receptive tissue. It is possible that
similar cells could contribute to the efficacy of L-DOPA in the treat
ment of Parkinson's disease.