Tyrosine hydroxylase, aromatic L-amino acid decarboxylase and dopamine metabolism after chronic treatment with dopaminergic drugs

Citation
S. Cho et al., Tyrosine hydroxylase, aromatic L-amino acid decarboxylase and dopamine metabolism after chronic treatment with dopaminergic drugs, BRAIN RES, 830(2), 1999, pp. 237-245
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
0006-8993 → ACNP
Volume
830
Issue
2
Year of publication
1999
Pages
237 - 245
Database
ISI
SICI code
0006-8993(19990605)830:2<237:THALAD>2.0.ZU;2-6
Abstract
Mice were treated with dopamine (DA) receptor agonist and antagonist drugs: Agonists: (+/-)-SKF 38393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3 -benza zepine-7, 8-diol) [DA D-1-like]; bromocriptine, [DA D-2 selective]; quinpir ole, [DA D-2/D-3 preferring]; (+/-)-7-hydroxy-dipropylamino-tetralin (7-OH- DPAT), [DA D-3/D-2 preferring], Antagonists: R(+)-SCH 23390 (R(+)-7-chloro- 8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine), [DA D-1-l ike]; and haloperidol, [DA D-2-like]. All drugs were administered intraperi toneally, two injections daily 8 h apart for 30 days. Aromatic L-amino acid decarboxylase (AAAD) and tyrosine hydroxylase (TH) activity, protein and m RNA, as well. as DA metabolism were followed with time thereafter in the ni grostriatal neurons. We observed that chronic administration of D-1-like ag onists had no effect on TH or AAAD activity, while D-2-like agonists decrea sed AAAD, but not TH activity. Additionally, chronic blockade of DA D-2-lik e receptors resulted in prolonged induction of TH and AAAD, while chronic b lockade of DA D-1-like receptors induced changes of AAAD only. Compared to TH the induction of AAAD was longer lasting. DA metabolism was altered by c hronic administration of drugs acting on DA D-2-like, but not DA D-1-like r eceptors, and in general the patterns of change did not follow those for TH or AAAD. When studied 48 h after the last dose of the chronic haloperidol schedule TH displayed tolerance to acute drug challenge. At the same time i nterval, there was tolerance to the enhancing effects of haloperidol and SC H 23390 on DA metabolism. The induction of AAAD by haloperidol or SCH 23990 did not appear to develop tolerance after chronic administration. These ob servations complement existing knowledge, and provide novel information abo ut AAAD that may have practical importance for Parkinson's patients on L-DO PA therapy. (C) 1999 Elsevier Science B.V. All rights reserved.