Regulation of striatal aromatic L-amino acid decarboxylase: effects of blockade or activation of dopamine receptors.
Previous experiments have shown that blockade of dopamine D1 or D2 receptors by SCH 23390 or pimozide increases aromatic L-amino acid decarboxylase (AADC) activity in the rat striatum and the mesolimbic system. This study examined whether other dopamine receptor antagonists affect AADC activity and if there is an interaction between dopamine D1 and D2 receptor blockade on AADC activity. The possible effect of dopamine receptor agonists on AADC activity has been investigated as well. Administration of cis-flupenthixol (0.5 and 1 mg/kg) increased striatal AADC activity (by 25 and 26% above controls) and similar effects were observed with remoxipride (0.5-4 mg/kg) (by 18-27% above controls). Pretreatment with cycloheximide (10 mg/kg) did not change the increases produced by cis-flupenthixol (0.5 mg/kg). The administration of non-neuroleptic trans-flupenthixol did not change AADC activity. Combined treatment with SCH 23390 (0.1 mg/kg) and remoxipride (0.5 mg/kg), but not combination of SCH 23390 (0.1 mg/kg) and pimozide (0.3 mg/kg), showed higher increases of AADC activity than by the individual treatments, suggesting an interaction between the effects of the two drugs. Bromocriptine, but not (-)-quinpirole and d-amphetamine, significantly reduced the striatal AADC activity by 23% at the dose of 10 mg/kg. The results further demonstrate that AADC is a regulated enzyme in the rat brain.
Zhu
M Y
MY
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Juorio
A V
AV
Paterson
I A
IA
Boulton
A A
AA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D003513:Cycloheximide / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D004873:Ergolines / Q000494:pharmacology; D005475:Flupenthixol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010868:Pimozide / Q000008:administration & dosage / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D017330:Remoxipride / Q000008:administration & dosage / Q000494:pharmacology; D013237:Stereoisomerism
D014150:Antipsychotic Agents; D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017330:Remoxipride; D010868:Pimozide; D019257:Quinpirole; D001971:Bromocriptine; D003513:Cycloheximide; D001142:Aromatic-L-Amino-Acid Decarboxylases; D005475:Flupenthixol; D003913:Dextroamphetamine