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

M J Bannon,J M Lee,P Giraud,A Young,H U Affolter,T I Bonner

doi:10.1016/s0021-9258(19)62663-3

Abstract

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.

Highlights

Decreases Substance P, Substance K, and Preprotachykinin mRNAs substance P release (2, 3)
Decreased preprotachykininmRNAs and tachykinins Radioimmunoassays-Tissues were extracted and substance P-like apparently parallels the period of maximum risk for immunoreactivity and substance K-like immunoreactivity were asthe development of certain antipsychotic drug-inducesdayed by radioimmunoassay as previously described (12-14)
Pre- carrier, and thesamples were extracted 2-3 times with 2 volumes of vious studies have shown that therepeated administration of dopamine antagonistdrugs decreases the concentration of substance P in the substantia nigra (2-6)

Summary

Introduction

Decreases Substance P, Substance K, and Preprotachykinin mRNAs substance P release (2, 3). Splicing encode for either substance P alone ( a preprotachykinin mRNA) or for both substance P and the newly discov- From the mepartment of Psychiatry, Yale University and chronic effects of the antipsychotic drug haloperidol on Schoolof Medicine and the Abraham Ribicoff Research the levels of striatonigral preprotachykinin mRNAs Tachykinin-encoding mRNAs rapidly decreased after haloperidol, followed bydecreased tachykinin peptides, suggesting

Results

Conclusion