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J. Biol. Chem., Vol. 261, Issue 15, 6640-6642, May, 1986

Dopamine antagonist haloperidol decreases substance P, substance K, and preprotachykinin mRNAs in rat striatonigral neurons

MJ Bannon, JM Lee, P Giraud, A Young, HU Affolter and TI Bonner

Rat genomic clones were used to quantitate preprotachykinin mRNAs in the rat basal ganglia, while the tachykinin peptide products substance P and substance K were measured by radioimmunoassay. Administration of the dopamine antagonist (antipsychotic) drug haloperidol significantly decreased substance P, substance K, and both alpha (substance P encoding) and beta (substance P/substance K encoding) preprotachykinin mRNAs, suggesting a drug-induced decrease in striatonigral tachykinin biosynthesis. The time course for decreased preprotachykinin mRNAs and tachykinins apparently parallels the period of maximum risk for the development of certain antipsychotic drug-induced extrapyramidal side effects seen clinically. Tachykinin interaction with dopamine neurons may play an important role in the modulation of basal ganglia function.
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