Mice lacking PKCγ exhibit decreased anxiety

Mice lacking PKCγ exhibit decreased anxiety
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DOI:
10.1023/a:1001951104208
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发表时间:
2000-03-01
期刊:
影响因子:
2.6
通讯作者:
Wehner, JM
Wehner, JM
中科院分区:
医学3区
文献类型:
--
作者:
Bowers, BJ;Collins, AC;Wehner, JM

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为了探讨蛋白激酶C(PKC)的蛋白激酶C(PKC)亚型在调节焦虑的神经化学通路中的作用,对缺乏PKCγ编码基因的小鼠进行了三种接近回避焦虑测试,包括杂合子和野生型。零突变小鼠在高架正迷宫、黑白盒和镜像室中的基线焦虑相关行为持续减少。在高架的正迷宫中,突变小鼠进入张开双臂的次数明显增加,在迷宫的张开双臂中花费的时间也更多。在黑白盒中,零突变小鼠的隔室之间的转换最大,而在镜像小室中,突变小鼠明显不那么焦虑,进入的潜伏期显著减少,在小室中花费的时间更长。迷宫中的运动活动指数和家庭笼子中的活动测试表明,在突变小鼠中观察到的焦虑减轻并不是由于不同基因型之间的基线运动活动差异。这些结果表明,PKC-γ可能通过其对GABA(A)和5-HT2受体的突触后调节而被认为是焦虑症的病因之一。
To investigate the contribution of the PKC gamma isoform of protein kinase C (PKC) in neurochemical pathways regulating anxiety, mice lacking the gene encoding PKC gamma were tested with heterozygote and wild-type littermates in three approach-avoidance tests of anxiety. Null mutant mice consistently displayed a decrease in baseline anxiety-related behaviors in the elevated plus-maze, the black/white box, and the mirrored chamber. In the elevated plus-maze, mutant mice entered the open arms significantly more often and spent more time in the open arms of the maze. In the black/white box, transitions between the compartments were greatest in the null mutant mice, and in the mirrored chamber, mutant mice were markedly less anxious with significantly decreased latencies to enter and more time spent in the chamber. Indices of locomotor activity in the mazes and tests of activity in home cages indicated that the reduced anxiety observed in the mutant mice was not due to baseline locomotor activity differences among the genotypes. These results suggest that PKC gamma be considered as one factor in the etiology of anxiety, perhaps via its post-synaptic regulation of GABA(A) and 5-HT2 receptors, two receptors implicated in the neurobiology of anxiety.