Chronic Morphine Treatment Switches the Effect of Dopamine on Excitatory Synaptic Transmission from Inhibition to Excitation in Pyramidal Cells of the Basolateral Amygdala
Chronic Morphine Treatment Switches the Effect of Dopamine on Excitatory Synaptic Transmission from Inhibition to Excitation in Pyramidal Cells of the Basolateral Amygdala
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慢性吗啡治疗将多巴胺对基底外侧杏仁核锥体细胞兴奋性突触传递的影响从抑制转变为兴奋
DOI：
10.1523/jneurosci.3806-11.2011
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发表时间：
2011-11-30
影响因子：
5.3
通讯作者：
Zheng, Ping
中科院分区：
文献类型：
--
作者：
Li, Zicheng;Luan, Wenjie;Zheng, Ping
基底外侧杏仁核（BLA）中的多巴胺能信号对于引发药物寻求行为复发的药物刺激学习非常重要。然而，对慢性吗啡治疗后该信号通路的适应性变化知之甚少。本研究采用全细胞膜片钳法观察慢性吗啡治疗对多巴胺（DA）对BLA锥体细胞兴奋性传递的影响。并结合生物化学和行为学技术对其作用机制和意义进行了研究。结果表明，慢性吗啡暴露使DA对兴奋性突触传递的作用由抑制转变为兴奋；慢性吗啡诱导的对DA作用的转换作用是由于其对D1受体的影响；慢性吗啡治疗对D1受体的影响位点在突触前；慢性吗啡治疗导致大鼠BLA突触体和突触体膜组分中D1受体的表达量显著增加；慢性吗啡治疗后D1受体激动剂对突触前谷氨酸释放的增强依赖于camp依赖性蛋白激酶的激活；bla内注射D1受体拮抗剂可消除吗啡依赖大鼠的条件性地方厌恶（CPA）。综上所述，在吗啡依赖大鼠中，慢性吗啡治疗可使DA通过突触前D1受体数量增加介导的BLA锥体细胞谷氨酸释放，将DA对兴奋性突触传递的作用从抑制转变为兴奋，阻断BLA D1受体可取消CPA。
Dopaminergic signaling in the basolateral amygdala (BLA) is important for drug-stimulus learning that triggers relapse to drug-seeking behavior. However, little is known about adaptive changes in this signaling pathway upon chronic morphine treatment. In this paper, we observed the influence of chronic morphine treatment on the effect of dopamine (DA) on the excitatory transmission in the pyramidal cells of BLA in slices with the whole-cell patch-clamp method. We also studied its mechanism and significance with pharmacological approaches combined with biochemical and behavioral techniques. The results showed that chronic morphine exposure switched the effect of DA on the excitatory synaptic transmission from inhibition to excitation; the chronic morphine-induced switching action on the effect of DA was due to its influence on D1 receptors; the site of the effect of chronic morphine treatment on D1 receptors was at presynaptic locus; chronic morphine treatment induced a significant increase in the amount of D1 receptor expression in the synaptosomes and synaptosomal membrane fraction from BLA; the enhancement of presynaptic glutamate release by D1 receptor agonist upon chronic morphine treatment was dependent on the activation of cAMP-dependent protein kinase; and the intra-BLA injection of D1 receptor antagonist canceled the conditioned place aversion (CPA) in morphine-dependent rats. In conclusion, chronic morphine treatment switches the effect of DA on the excitatory synaptic transmission from inhibition to excitation by the presynaptic D1 receptor amount increase-mediated glutamate release in the pyramidal cells of BLA and the blockade of D1 receptors in BLA cancels CPA in morphine-dependent rats.