Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum
| Autor: | Päivi Tuomainen, Pekka T. Männistö, S Kaakkola, R J Wurtman |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Microdialysis medicine.medical_specialty 3 4-Dihydroxyphenylacetic acid Dopamine Hypothalamus Striatum Pharmacology Levodopa 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Biological Psychiatry 030304 developmental biology 0303 health sciences Aromatic L-amino acid decarboxylase General Neuroscience Homovanillic acid Carbidopa Homovanillic Acid Rats Inbred Strains Corpus Striatum Rats 3. Good health Perfusion Psychiatry and Mental health Endocrinology nervous system Neurology chemistry Depression Chemical Catecholamine 3 4-Dihydroxyphenylacetic Acid Tyrosine Neurology (clinical) Dialysis Injections Intraperitoneal 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Neural Transmission - Parkinson's Disease and Dementia Section. 4:143-154 |
| ISSN: | 1435-1463 0936-3076 |
| DOI: | 10.1007/bf02251477 |
| Popis: | Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 micrograms/ml, or about 2% of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5% and 1.5%, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33% and 16%, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceeding 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD. |
| Databáze: | OpenAIRE |
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