Neurokinin-1 receptor-expressing neurons in the amygdala modulate morphine reward and anxiety behaviors in the mouse
Neurokinin-1 receptor-expressing neurons in the amygdala modulate morphine reward and anxiety behaviors in the mouse
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DOI：
10.1523/jneurosci.23-23-08271.2003
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发表时间：
2003-09-10
影响因子：
5.3
通讯作者：
Hunt, SP
中科院分区：
文献类型：
--
作者：
Gadd, CA;Murtra, P;Hunt, SP
缺乏神经激肽-1(NK1)受体(神经肽P物质(SP)的首选受体)的小鼠，不会表现出许多与吗啡奖赏相关的行为。为了确定可能对这种效应做出贡献的大脑区域，我们评估了使用神经毒素物质P-Saporin消融小鼠大脑特定区域表达NK1受体的神经元的行为影响。在初步研究中，双侧切除杏仁核中的这些神经元，而不是伏隔核和背内侧尾壳核，导致了吗啡奖励行为的减少。随后，在条件性位置偏爱(CPP)之前，用高架加迷宫(EPM)评估这些神经元在杏仁核内消融对焦虑行为的影响，并测量对吗啡的运动反应。杏仁核中表达NK1受体的神经元的缺失会导致大脑皮质焦虑样行为的增加。与生理盐水对照组相比，它还降低了吗啡CPP评分和急性吗啡给药的刺激效应，但不影响CPP对可卡因的作用。因此，小鼠杏仁核中表达NK1受体的神经元调节吗啡的奖赏行为。这些观察结果反映了在NK1受体敲除(NK1-/-)小鼠中观察到的结果，并表明杏仁核是SP和NK1受体在阿片类药物的动机特性中的作用以及与焦虑相关的行为控制的重要区域。
Mice lacking the neurokinin-1 (NK1) receptor, the preferred receptor for the neuropeptide substance P (SP), do not show many of the behaviors associated with morphine reward. To identify the areas of the brain that might contribute to this effect, we assessed the behavioral effects of ablation of neurons expressing the NK1 receptor in specific regions of the mouse brain using the neurotoxin substance P-saporin. In a preliminary investigation, bilateral ablation of these neurons from the amygdala, but not the nucleus accumbens and dorsomedial caudate putamen, brought about reductions in morphine reward behavior. Subsequently, the effect of ablation of these neurons in the amygdala on anxiety behavior was assessed using the elevated plus maze (EPM), before conditioned place preference (CPP), and locomotor responses to morphine were measured. Loss of NK1 receptor-expressing neurons in the amygdala caused an increase in anxiety-like behavior on the EPM. It also brought about a reduction in morphine CPP scores and the stimulant effect of acute morphine administration relative to saline controls, without affecting CPP to cocaine. NK1 receptor-expressing neurons in the mouse amygdala therefore modulate morphine reward behaviors. These observations mirror those observed in NK1 receptor knock-out (NK1-/-) mice and suggest that the amygdala is an important area for the effects of SP and the NK1 receptor in the motivational properties of opiates, as well as the control of behaviors related to anxiety.