Morphine-Induced Dendritic Spine Remodeling in Rat Nucleus Accumbens Is Corticosterone Dependent
Morphine-Induced Dendritic Spine Remodeling in Rat Nucleus Accumbens Is Corticosterone Dependent
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DOI：
10.1093/ijnp/pyz014
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发表时间：
2019-06-01
影响因子：
4.8
通讯作者：
Noble, Florence
中科院分区：
文献类型：
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作者：
Geoffroy, Helene;Canestrelli, Corinne;Noble, Florence
背景：慢性吗啡处理对大鼠伏隔核等多个脑区产生重要的形态变化。方法：本研究观察了在末次注射吗啡(5 mg/kg，每日1次，共14天)后1天，相对小剂量的慢性吗啡处理对大鼠伏隔核核心和壳层中棘神经元形态的影响。用1，1‘dioctadecyl-3，3，3’，3‘-tetramethylindocarbocyanine高氯酸盐晶体标记中棘神经元，并用激光共聚焦扫描显微镜进行分析。结果：与对照组相比，吗啡处理组大鼠的壳层中的细刺增多，短刺减少。由于吗啡处理的大鼠也表现出血浆皮质酮水平的升高，我们探讨了吗啡处理引起的伏隔核脊髓改变是否会受到激素耗竭的影响。因此，双侧肾上腺切除的大鼠在相同的条件下接受吗啡治疗。在皮质酮缺乏的吗啡处理大鼠中，壳中的短刺没有更多的变化，而壳中的蘑菇刺和核心中的短刺显著增加。在细刺方面，与生理盐水相比，去肾上腺大鼠肾上腺切除后，吗啡增加的程度低于非去肾上腺动物。结论：慢性低剂量吗啡处理后伏隔核树突棘重塑依赖于皮质酮水平。
Background: Chronic morphine treatments produce important morphological changes in multiple brain areas including the nucleus accumbens.Methods: In this study, we have investigated the effect of chronic morphine treatment at a relatively low dose on the morphology of medium spiny neurons in the core and shell of the nucleus accumbens in rats 1 day after the last injection of a chronic morphine treatment (5 mg/kg once per day for 14 days). Medium spiny neurons were labeled with 1,1' dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate crystal and analyzed by confocal laser-scanning microscope.Results: Our results show an increase of thin spines and a decrease of stubby spines specifically in the shell of morphine-treated rats compared with control. Since morphine-treated rats also presented an elevation of corticosterone level in plasma, we explored whether spine alterations induced by morphine treatment in the nucleus accumbens could be affected by the depletion of the hormone. Thus, bilaterally adrenalectomized rats were treated with morphine in the same conditions. No more alteration in stubby spines in the shell was detected in morphine-treated rats with a depletion of corticosterone, while a significant increase was observed in mushroom spines in the shell and stubby spines in the core. Regarding the thin spines, the increase observed with morphine compared with saline was lower in adrenalectomized rats than in nonadrenalectomized animals.Conclusion: These results indicate that dendritic spine remodeling in nucleus accumbens following chronic morphine treatment at relatively low doses is dependent on corticosterone levels.