Lithium augments pilocarpine-induced fos gene expression in rat brain

Elyse D. Weiner, Vasundhara D. Kalasapudi, Demitri F. Papolos, Herbert M. Lachman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Lithium salts are considered the most effective agents used in treating manic-depression. Previous studies in PC12 pheochromocytoma cells indicate that lithium has a dramatic augmenting effect on expression of the fos proto-oncogene, a component of the AP-1 transcription factor. Although fos expression is activated by agonists that function through different signal transduction pathways, the lithium augmenting effect appears to be specific for receptor and post-receptor stimulators of protein kinase C (PKC). In particular, fos induction mediated by the m1 muscarinic receptor linked to PKC activation was found to be exquisitely sensitive to lithium enhancement. We now show that a similar augmenting effect can be demonstrated in rat brain. Following treatment with the muscarinic agonist pilocarpine, fos mRNA accumulates in the cortex, an effect that is blocked by the m1 antagonist pirenzepine. Rats treated with a single intraperitoneal injection of lithium chloride exhibited a substantial increase in pilocarpine-mediated fos expression. In contrast, fos expression induced in several brain regions by a single electroconvulsive shock is not augmented by lithium. The finding that short-term treatment with lithium enhances fos expression in the brain suggests a mechanism for its therapeutic action.

Original languageEnglish (US)
Pages (from-to)117-122
Number of pages6
JournalBrain Research
Volume553
Issue number1
DOIs
StatePublished - Jul 5 1991

Keywords

  • Lithium
  • Manic-depression
  • Muscarinic cholinergic
  • Pilocarpine
  • Protein kinase C
  • fos proto-oncogene

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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