L-3,4-dihydroxyphenylalanine-induced c-Fos expression in the CNS under inhibition of central aromatic L-amino acid decarboxylase.
L-3,4-dihydroxyphenylalanine (DOPA) is a neurotransmitter candidate. To map the DOPAergic system functionally, DOPA-induced c-Fos expression was detected under inhibition of central aromatic L-amino acid decarboxylase (AADC). In rats treated with a central AADC inhibitor, DOPA significantly increased the number of c-Fos-positive nuclei in the paraventricular nuclei (PVN) and the nucleus tractus solitarii (NTS), and showed a tendency to increase in the supraoptic nuclei (SON), but not in the striatum. On the other hand, DOPA with a peripheral AADC inhibitor elevated the level of c-Fos-positive nuclei in the four regions, suggesting that DOPA itself induces c-Fos expression in the SON, PVN and NTS. In rats treated with 6-hydroxydopamine (6-OHDA) to lesion the nigrostriatal dopamine (DA) pathway, DOPA significantly induced c-Fos expression in the four regions under the inhibition of peripheral AADC. However, under the inhibition of central AADC, DOPA did not significantly increase the number of c-Fos-positive nuclei in the four regions, suggesting that DOPA at least in part induces c-Fos expression through its conversion to DA. It was likely that the 6-OHDA lesion enhanced the response to DA, but attenuated that to DOPA itself. In conclusion, we proposed that the SON, PVN and NTS include target sites for DOPA itself.
Shimamura
M
M
Department of Neurology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Shimizu
M
M
Yagami
T
T
Funabashi
T
T
Kimura
F
F
Kuroiwa
Y
Y
Misu
Y
Y
Goshima
Y
Y
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001545:Benserazide / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D002490:Central Nervous System / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects*; D006834:Hydrazines / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D006834:Hydrazines; D016760:Proto-Oncogene Proteins c-fos; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; C004297:3-hydroxybenzylhydrazine; D001142:Aromatic-L-Amino-Acid Decarboxylases