Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice

Monique R. Adams, Eugene P. Brandon, Elena H. Chartoff, Rejean L. Idzerda, Daniel Dorsa, G. Stanley Mcknight

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The antipsychotic drug, haloperidol, elicits the expression of neurotensin and c-fos mRNA in the dorsal lateral region of the striatum and produces an acute cataleptic response in rodents that correlates with the motor side effects of haloperidol in humans. Mice harboring a targeted disruption of the RIIβ subunit of protein kinase A have a profound deficit in cAMP-stimulated kinase activity in the striatum. When treated with haloperidol, RIIβ mutant mice fail to induce either c-fos or neurotensin mRNA and the acute cataleptic response is blocked. However, both wild-type and mutant mice become cataleptic when neurotensin peptide is directly injected into the lateral ventricle, demonstrating thai the kinase deficiency does not interfere with the action of neurotensin but rather its synthesis and release. These results establish a direct role for protein kinase A as a mediator of haloperidol induced gene induction and cataleptic behavior.

Original languageEnglish (US)
Pages (from-to)12157-12161
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number22
DOIs
StatePublished - Oct 28 1997
Externally publishedYes

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Catalepsy
Neurotensin
Haloperidol
Cyclic AMP-Dependent Protein Kinases
Gene Expression
Phosphotransferases
Messenger RNA
Lateral Ventricles
Antipsychotic Agents
Rodentia
Peptides
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice. / Adams, Monique R.; Brandon, Eugene P.; Chartoff, Elena H.; Idzerda, Rejean L.; Dorsa, Daniel; Mcknight, G. Stanley.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 22, 28.10.1997, p. 12157-12161.

Research output: Contribution to journalArticle

Adams, Monique R. ; Brandon, Eugene P. ; Chartoff, Elena H. ; Idzerda, Rejean L. ; Dorsa, Daniel ; Mcknight, G. Stanley. / Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 22. pp. 12157-12161.
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