Tachykinins in the rat substantia nigra: effects of selective dopamine receptor antagonists.
The effects of sustained blockade of dopamine receptors by selective dopamine antagonists on the tachykinin (substance P and neurokinin A) content in the substantia nigra were examined. The treatment of rats for 14 days with D-1/D-2 dopamine receptor antagonist haloperidol (2 mg/kg) or selective D-2 antagonist sulpiride (100 mg/kg) produced a similar and significant decrease in nigral substance P and neurokinin A-like immunoreactivity content, about 32-36% and 27-28% of control respectively. In contrast, administration of SCH 23390 (1 mg/kg), a selective and potent D-1 dopamine receptor antagonist, failed to affect the levels of substance P and neurokinin A in the substantia nigra and did not change the sulpiride-induced reduction of the nigral tachykinin peptides. These results indicate that the D-1 dopamine receptors are not involved in the modulation of nigral substance P and neurokinin A content and suggest that the blockade of the D-2 dopamine receptor subtype exerts the same regulation of the tachykinin gene expression, in spite of the existence of three mRNAs encoding substance P and neurokinin A.
Oblin
A
A
Synthélabo Recherche (LERS), Bagneux, France.
Zivkovic
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D015287:Neurokinin B / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D015320:Tachykinins / Q000378:metabolism*
D001552:Benzazepines; D018492:Dopamine Antagonists; D015320:Tachykinins; D013373:Substance P; D013469:Sulpiride; D015287:Neurokinin B; D006220:Haloperidol