Strain differences in lithium attenuation of d-amphetamine-induced hyperlocomotion:: A mouse model for the genetics of clinical response to lithium
Strain differences in lithium attenuation of d-amphetamine-induced hyperlocomotion:: A mouse model for the genetics of clinical response to lithium
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DOI：
10.1038/sj.npp.1301254
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发表时间：
2007-06-01
影响因子：
7.6
通讯作者：
Manji, Husseini K.
中科院分区：
文献类型：
--
作者：
Gould, Todd D.;O'Donnell, Kelley C.;Manji, Husseini K.
锂对兴奋剂引起的过度运动的衰减是一种啮齿动物模型，可能有助于了解锂的治疗作用机制和开发新型锂模拟化合物。为了为未来研究锂作为治疗剂的神经生物学和遗传学研究奠定基础，我们研究了锂对 12 只（3 个远交系）小鼠品系的 d-苯丙胺诱导的过度运动的影响。在我们的初步筛选中，小鼠接受（1）不接受任何药物，（2）仅接受氯化锂，（3）仅接受 d-苯丙胺，或（4）接受 d-苯丙胺和氯化锂。虽然单独使用 LiCl 对任何菌株的运动都没有显着影响，但 LiCl 与 d-安非他明联合使用时，菌株的影响存在很大程度的差异。 LiCl 减弱了 C57BL/6J、C57BL/6Tac、Black Swiss 和 CBA/J 小鼠中 d-苯丙胺诱导的过度运动，而对 d-苯丙胺有反应的 CD-1、FVB/NJ、SWR/J 和 NIH Swiss 小鼠则没有表现出 LiCl 的显着影响。通过锂预处理，d-安非他明诱导的 C3H/HeJ 菌株的过度运动增加。在进行丹非他明攻击之前，对一部分菌株进行了 4 周的碳酸锂治疗，在这些菌株中，锂产生的效果与急性给药后所观察到的效果相同。对锂的应变反应不依赖于 d-苯丙胺或 LiCl 的剂量。此外，这些结果并不能用大脑中的锂水平来解释，这表明对锂的这些行为反应受到固有遗传或其他特定于锂对大脑功能影响的生物机制的控制。
Lithium attenuation of stimulant-induced hyperlocomotion is a rodent model that may be useful both to understand the mechanism of the therapeutic action of lithium and to develop novel lithium-mimetic compounds. To lay the foundation for future investigations into the neurobiology and genetics of lithium as a therapeutic agent, we studied the effect of lithium on d-amphetamine-induced hyperlocomotion in 12 ( 3 outbred) mouse strains. In our initial screening, mice received either ( 1) no drugs, ( 2) LiCl only, ( 3) d-amphetamine only, or ( 4) d-amphetamine and LiCl. Whereas there was no significant effect of LiCl alone on locomotion in any strain, there was a large degree of strain variation in the effects of LiCl combined with d-amphetamine. LiCl attenuated d-amphetamine-induced hyperlocomotion in C57BL/6J, C57BL/6Tac, Black Swiss, and CBA/J mice, whereas CD-1, FVB/NJ, SWR/J, and NIH Swiss mice, which were responsive to d-amphetamine, showed no significant effect of LiCl. d-Amphetamine-induced hyperlocomotion in the C3H/HeJ strain was increased by pretreatment with lithium. A subset of strains were treated for 4 weeks with lithium carbonate before the damphetamine challenge, and in each of these strains, lithium produced effects identical to those seen following acute administration. Strain responsiveness to lithium was not dependent upon the dose of either d-amphetamine or LiCl. Further, the results are not explained by brain lithium levels, which suggests that these behavioral responses to lithium are under the control of inherent genetic or other biological mechanisms specific to the effects of lithium on brain function.