An autoradiographic study of [3H]AMPA receptor binding and in situ hybridization of AMPA sensitive glutamate receptor A (GluR-A) subunits following morphine withdrawal in the rat brain
An autoradiographic study of [3H]AMPA receptor binding and in situ hybridization of AMPA sensitive glutamate receptor A (GluR-A) subunits following morphine withdrawal in the rat brain
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DOI：
10.1016/s0361-9230(00)00261-6
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发表时间：
2000-06-01
影响因子：
3.8
通讯作者：
Ho, IK
中科院分区：
文献类型：
--
作者：
Jang, CG;Rockhold, RW;Ho, IK
众所周知，长期使用阿片类药物会导致身体依赖性的发展。最近，阿片类药物戒断综合征的表达涉及到阿片类药物的代谢机制。为了更好地研究多巴胺能参与，放射自显影研究[H-3]AMPA受体结合和AMPA敏感性谷氨酸受体A（GluR-A）亚基在大鼠脑中的原位杂交的评估，分别进行7小时后，从吗啡输注撤出。通过脑室内（i. c. v.）通过渗透微泵输注吗啡（26 nmol/μ l/h）3天。将14 μ m厚的脑切片与15 nM [H-3]AMPA孵育，以定量与AMPA受体的结合。原位杂交探针的3'端用末端脱氧核苷酸转移酶和[S-35]dATP标记。吗啡戒断后，[H-3]AMPA结合的程度在大鼠皮质区（18-21%）、尾壳核（20%）和海马（7-9%）显著增加。GluR-A、flop和flip亚基的mRNA水平最高，分别位于海马的齿状回和CA 3区。在大鼠脑海马CA 3区（8%），谷氨酰胺受体-A的翻转形式的mRNA水平降低。在顶叶皮层（7%）和内嗅皮层（8%）中，GluR-A翻转形式的mRNA水平增加。[H-3]AMPA与其受体结合的增加可能在吗啡依赖戒断过程中起重要作用。(C)2000 Elsevier Science Inc.
Chronic treatment with opioids is well known to result in the development of physical dependence. More recently, glutamatergic mechanisms have been implicated in expression of the withdrawal syndrome from opioids. To better examine glutamatergic involvement, an autoradiographic study of [H-3]AMPA receptor binding and an assessment of in situ hybridization of AMPA sensitive glutamate receptor A (GluR-A) subunits in the rat brain were each performed 7 h after withdrawal from morphine infusion. Animals were rendered dependent by intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/mu l/h) via osmotic minipumps for 3 days. Brain sections of 14-mu m thickness were incubated with 15 nM [H-3]AMPA for quantitation of binding to the AMPA receptor. The probe for in situ hybridization was labeled at its 3' end using terminal deoxynucleotidyl transferase and [S-35]dATP, The highest degree of [H-3]AMPA binding was shown in the hippocampus. The extent of [H-3]AMPA binding was increased significantly in the cortex areas (18-21%), caudate-putamen (20%), and hippocampus (7-9%) of rats following withdrawal from morphine. The highest levels of mRNA for GluR-A, flop and flip subunits, were found in the dentate gyrus and in the CA3 region of the hippocampus, respectively. The levels of mRNA for the flop form of GluR-A were decreased in the CA3 of hippocampus (8%) of the rat brain. The levels of mRNA for the flip form of GluR-A were increased in the parietal cortex (7%) and the entorhinal cortex (8%). Increases in the binding of [H-3]AMPA to its receptor may play an important role during withdrawal from morphine dependence. (C) 2000 Elsevier Science Inc.