Facultad de Ciencias, Instituto de Investigación Biomédica, Universidad de Málaga, 29071 Málaga, Spain.
Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
Cells. 2021 Dec 23;11(1):31. doi: 10.3390/cells11010031.
Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D receptor (DR) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the DR agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of DR modulating morphine-induced plasticity in the dorsal striatum. Thus, DR could represent a valuable pharmacological target for the safety use of morphine in pain management.
长期接触吗啡会引起大脑中与奖励相关区域的结构和突触可塑性，这在成瘾中起着关键作用。然而，尽管背侧纹状体在药物相关习惯学习中起着关键作用，但对其吗啡诱导的神经适应性的研究还很少。在这里，我们表明，长期吗啡处理会触发背侧纹状体投射神经元（MSNs）树突棘的回缩和丢失。为了扩展以前的发现，我们还探讨了多巴胺 D 受体（DR）是否可以调节纹状体中吗啡诱导的可塑性。吗啡与 DR 激动剂 PD168,077 的联合治疗会导致 MSNs 树突棘的扩展，并恢复树突棘密度。在电生理水平上，PD168,077 与吗啡联合使用会改变 MSNs 的电特性并降低其兴奋性。最后，来自黑质的结果表明，PD168,077 可以抵消吗啡诱导的纹状体向黑质投射中的 μ 阿片受体（MOR）上调和多巴胺能细胞中 G 蛋白门控内向整流钾通道（GIRK1 和 GIRK2）的下调。这些结果强调了 DR 调节吗啡诱导的背侧纹状体可塑性的关键作用。因此，DR 可能成为安全使用吗啡治疗疼痛的有价值的药理学靶点。
