Dopamine D3 receptor antisense influences dopamine synthesis in rat brain.
Intracerebroventricular infusion of an all-phosphorothioate antisense oligodeoxynucleotide targeted at the rat dopamine D3 receptor mRNA (10 micrograms h-1, 5 days) resulted in a significant reduction (19%) of the binding of the [D2 + D3] ligand [3H]spiperone in the limbic forebrain, where D3 receptors are relatively abundant, but not in caudate-putamen, where D3 receptors are sparse. In nucleus accumbens antisense treatment also caused an increase in dopamine synthesis; in contrast, antisense administration did not counteract the effect of apomorphine on dopamine formation. No effect of antisense administration on dopamine synthesis was observed in caudate-putamen. The results support the usefulness of the antisense strategy for the study of D3 receptors and suggest that D3 receptors may influence dopamine synthesis.
Nissbrandt
H
H
Department of Physiology and Pharmacology, Göteborg University, Sweden.
Ekman
A
A
Eriksson
E
E
Heilig
M
M
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000187:drug effects; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D004298:Dopamine / Q000096:biosynthesis*; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D012107:Research Design; D013134:Spiperone / Q000494:pharmacology; D013378:Substantia Nigra / Q000502:physiology
D016375:Antisense Elements (Genetics); D016376:Oligonucleotides, Antisense; D011954:Receptors, Dopamine; D013134:Spiperone; D001058:Apomorphine; D004298:Dopamine