Influence of monoamine oxidase inhibitors on striatonigral dynorphin system: a study with deprenyl and clorgyline.
Neuropeptides
; 25(1): 35-45, 1993 Jul.
Article
em En
| MEDLINE
| ID: mdl-7692341
ABSTRACT
This study examined the influence of selected monoamine oxidase (MAO) inhibitors on basal ganglia neurotransmitters (dopamine and 5-hydroxytryptamine) and neuropeptide (dynorphin) systems of Sprague-Dawley rats. The striatum or substantia nigra or both were used for biochemical determinations. The striatal concentrations of DA, 5-hydroxytryptamine (5-HT) and their metabolites were determined by HPLC. The levels of striatal and nigral dynorphin A (1-8) (DYN) were determined by radioimmunoassay. The abundance of striatal prodynorphin (PD) mRNA was determined by Northern blot analysis using a cRNA probe. Deprenyl, a MAO-B selective inhibitor (0.25, 0.5, 5, 10 or 20 mg/kg/day, subcutaneously (s.c.) for 4 d) and clorgyline, a MAO-A inhibitor (0.5, 5, 10 or 20 mg/kg/day, s.c. for 4 d) produced a dose-related increase in DA and 5-HT and a decrease in their metabolites in the striatum. Only high doses (20 mg/kg) of deprenyl or clorgyline induced an increase in DYN levels in the striatum and substantia nigra (DYN terminal region); the increased level of DYN was accompanied by an increase in PD-mRNA levels in striatum (DYN cell-body region). Co-administration of low doses (2.5 mg/kg/day, s.c. for 4 d) of deprenyl and clorgyline, that would selectively inhibit MAO-B and MAO-A respectively, produced a marked increase in DA and 5-HT, a decrease in DOPAC and 5-HIAA, an increase in DYN levels in the striatum and substantia nigra and an increase in PD-mRNA levels in the striatum. The results indicate that concurrent inhibition of MAO-B and MAO-A, that results in markedly elevated levels of DA and 5-HT in the striatum, is associated with an increase in dynorphin biosynthesis in the striatonigral neurons.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dinorfinas
/
Substância Negra
/
Dopamina
/
Serotonina
/
Corpo Estriado
/
Inibidores da Monoaminoxidase
Limite:
Animals
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article