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

被引:94
作者
Adams, MR
Brandon, EP
Chartoff, EH
Idzerda, RL
Dorsa, DM
McKnight, GS
机构
[1] UNIV WASHINGTON, DEPT PHARMACOL, SEATTLE, WA 98195 USA
[2] UNIV WASHINGTON, DEPT PSYCHIAT & BEHAV SCI, SEATTLE, WA 98195 USA
[3] UNIV WASHINGTON, GRAD PROGRAM NEUROBIOL & BEHAV, SEATTLE, WA 98195 USA
关键词
D O I
10.1073/pnas.94.22.12157
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 RII beta subunit of protein kinase A have a profound deficit in cAMP-stimulated kinase activity in the striatum, When treated with haloperidol, RII beta 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 that 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.
引用
收藏
页码:12157 / 12161
页数:5
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