Lithium increases rat striatal beta- and gamma-preprotachykinin messenger RNAs.
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.
Sivam
S P
SP
Department of Pharmacology and Toxicology, Northwest Center for Medical Education, Indiana University School of Medicine, Gary.
Krause
J E
JE
Takeuchi
K
K
Li
S
S
McGinty
J F
JF
Hong
J S
JS
D000818:Animals; D003342:Corpus Striatum / Q000032:analysis / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D007150:Immunohistochemistry; D008094:Lithium / Q000097:blood / Q000494:pharmacology*; D008297:Male; D015288:Neurokinin A / Q000032:analysis / Q000276:immunology; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D013373:Substance P / Q000032:analysis / Q000276:immunology; D015320:Tachykinins / Q000235:genetics*
D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D015288:Neurokinin A; D008094:Lithium; D006220:Haloperidol