Lithium increases rat striatal beta- and gamma-preprotachykinin messenger RNAs

S. P. Sivam, J. E. Krause, K. Takeuchi, S. Li, J. F. McGinty, J. S. Hong

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Previous reports indicate that the antimanic drug, lithium, increases substance P-like immunoreactivity (SP-LI) in the basal ganglia. The aim of this study was to use lithium as a pharmacological tool to further understand the mechanism of this process. We have used solution hybridization-nuclease protection assays to quantitate the specific preprotachykinin (PPT) mRNAs and radioimmunoassays and immunocytochemistry to assess SP-LI levels in the striatum of male Fisher F-344 rats. A regimen of subchronic administration of lithium (4 mEq/kg i.p. for 1, 2, 4 or 6 days) increased SP-LI in a time-dependent fashion. Concurrent administration of a dopamine receptor antagonist, haloperidol (1 mg/kg s.c. for 4 days) with a 4-day lithium regimen partially blocked the lithium-induced increase in SP-LI as well as neurokinin A-like immunoreactivity. An analysis of the abundance of individual PPT mRNAs indicated that lithium increases beta- and gamma-PPT mRNAs in the striatum; coadministration of haloperidol attenuates the lithium-induced increases. These results indicate that lithium affects the tachykinin biosynthetic process by accelerating transcriptional and/or translational processes in striatonigral neurons and that the dopaminergic system appears to be partly involved in this process.

Original languageEnglish (US)
Pages (from-to)1297-1301
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - 1989

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Sivam, S. P., Krause, J. E., Takeuchi, K., Li, S., McGinty, J. F., & Hong, J. S. (1989). Lithium increases rat striatal beta- and gamma-preprotachykinin messenger RNAs. Journal of Pharmacology and Experimental Therapeutics, 248(3), 1297-1301.