Long-term lithium treatment selectively reduces receptor-coupled inositol phospholipid hydrolysis in rat brain

Tamara L. Casebolt, Richard S. Jope

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Rats were treated with dietary lithium for 30 days, followed by assessment of the activity of the receptor-coupled inositol phospholipid second messenger-producing system in three brain regions. The major effect of long-term lithium treatment was a significant reduction of the response to norepinephrine in all three brain regions that were examined: the cerebral cortex, the hippocampus, and the striatum. After long-term lithium treatment, the response to serotonin was reduced in the hippocampus and striatum, but not the cortex, and the carbachol-induced response was only reduced in the striatum. Lithium treatment did not alter the incorporation of [3H] inositol into phospholipids, the in vitro lithium concentration-dependent accumulation of [3H]inositol monophosphate, or the stimulation by NaF of inositol phospholipid hydrolysis. These results indicate that the decreased responses to agonists after long-term lithium treatment are not likely to be due to depletion of inositol phospholipids or to altered activity of myo-inositol-1-phosphatase, phospholipase C, or the guanine nucleotide-binding protein. It is suggested that long-term lithium treatment may alter receptor number or receptor coupling, perhaps by phosphorylotion, thereby selectively lowering the agonist-induced generation of second messengers by the inositol phospholipid system.

Original languageEnglish (US)
Pages (from-to)329-340
Number of pages12
JournalBiological Psychiatry
Issue number3
StatePublished - Feb 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Biological Psychiatry


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