Mice Lacking the β4 Subunit of the Nicotinic Acetylcholine Receptor Show Memory Deficits, Altered Anxiety- And Depression-Like Behavior, and Diminished Nicotine-Induced Analgesia

Abstract

Rationale: The role of β4-containing nicotinic acetylcholine receptors (nAChRs) in cognition, anxiety, depression, and analgesia in the absence of nicotine is unclear.

Methods: Wild-type (β4(+/+)) and knockout (β4(-/-)) mice for the nAChR β4 subunit were tested in behavioral tests assessing cognitive function, affective behaviors, and nociception.

Results: There were no learning and memory deficits in β4(-/-) mice compared with β4(+/+) mice during the acquisition of the Barnes maze, contextual fear conditioning, and Y maze tasks. In the Barnes maze memory retention test, male β4(-/-) mice showed reduced use of the spatial search strategy, indicating small spatial memory deficits compared with β4(+/+) mice. In the cue-induced fear conditioning memory retention test, β4(-/-) mice exhibited reduced freezing time compared with β4(+/+) mice. Compared with β4(+/+) mice, β4(-/-) mice exhibited decreased anxiety-like behavior in the light-dark box. Depression-like behavior in β4(-/-) mice was decreased in the tail suspension test and increased in the forced swim test compared with β4(+/+) mice. β4(-/-) mice did not differ from β4(+/+) mice in basal nociception but were less sensitive to the antinociceptive effect of nicotine in 2 tests of acute thermal pain.

Conclusions: Lack of β4-containing nAChRs resulted in small deficits in hippocampus- and amygdala-dependent memory retention functions. β4-containing nAChRs are involved in anxiety- and depression-like behaviors and contribute to the analgesic effects of nicotine.

缺乏β4 nAchRs (一种受体蛋白)的老鼠没有出现学习和记忆的障碍（通过Barnes maze, contextual fear conditioning, and Y maze tasks实验检测）；

相比于野生型，β4-ko小鼠的焦虑样行为减少（在light-dark box测试中），这里给出的抑郁样行为的结论相矛盾，在悬尾实验中抑郁样行为减少，而在强迫游泳中抑郁样行为却增加—不知道这种矛盾的结论作者是怎么解释的，杂志又怎么能接受这种矛盾的结论发表的，明天细看一下文章。

作者给出的结论中有关抑郁症的部分：含β4的nAChR参与焦虑和抑郁样行为。

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