Gadd Christopher A, Murtra Patricia, De Felipe Carmen, Hunt Stephen P
Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom.
J Neurosci. 2003 Sep 10;23(23):8271-80. doi: 10.1523/JNEUROSCI.23-23-08271.2003.
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.
缺乏神经激肽-1（NK1）受体的小鼠不会表现出许多与吗啡奖赏相关的行为，神经激肽-1受体是神经肽P物质（SP）的首选受体。为了确定可能导致这种效应的脑区，我们使用神经毒素P物质-皂草素评估了在小鼠脑特定区域消融表达NK1受体的神经元的行为效应。在一项初步研究中，双侧消融杏仁核而非伏隔核和背内侧尾状壳核中的这些神经元，会导致吗啡奖赏行为减少。随后，在进行条件性位置偏爱（CPP）之前，使用高架十字迷宫（EPM）评估杏仁核中这些神经元的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受体的神经元缺失导致在EPM上焦虑样行为增加。相对于生理盐水对照组，它还导致吗啡CPP评分降低以及急性给予吗啡的兴奋效应降低，而不影响对可卡因的CPP。因此，小鼠杏仁核中表达NK1受体的神经元调节吗啡奖赏行为。这些观察结果与在NK1受体基因敲除（NK1-/-）小鼠中观察到的结果相似，表明杏仁核是SP和NK1受体在阿片类药物动机特性以及与焦虑相关行为控制中发挥作用的重要区域。
