Contrasting effects of μ opioid receptor and δ opioid receptor deletion upon the behavioral and neurochemical effects of cocaine
Contrasting effects of μ opioid receptor and δ opioid receptor deletion upon the behavioral and neurochemical effects of cocaine
复制标题
DOI：
10.1016/j.neuroscience.2004.05.021
复制
发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Shippenberg, TS
中科院分区：
文献类型：
--
作者：
Chefer, VI;Kieffer, BL;Shippenberg, TS
用常规脑微透析方法检测野生型(WT)C57BL/6J小鼠和结构性缺失(MOR或DOR基因敲除[KO])小鼠伏隔核多巴胺(DA)水平。对这些动物的运动活动进行了评估。相对于MOR KO，DOR KO小鼠的基础运动活动增强，但与WT小鼠没有区别。注射生理盐水后，DOR小鼠，而不是WT或MOR KO小鼠的活动显著增加。急性注射可卡因使这三种基因的运动活动呈剂量相关的增加。低剂量(10 mg/kg)可卡因对DOR-KO小鼠的运动激活作用增强，而低剂量(20 mg/kg)和高剂量(20 mg/kg)的可卡因对MOR-KO动物的运动激活作用均减弱。微透析研究显示不同基因型之间的基础DA水平没有差异。急性给予可卡因，而不是生理盐水，可增加WT和KO动物的DA水平。然而，矛盾的是，与WT或MORKO相比，DOR KO的这种效应的幅度更小。这些数据表明，MOR或DOR的结构性缺失导致了对可卡因反应的不同影响，这与先前为这些突变体描述的不同表型一致。爱思唯尔有限公司代表伊布罗出版。
Conventional brain microdialysis was used to assess basal and cocaine-induced dopamine (DA) levels in the nucleus accumbens of wildtype (WT) C57BL/6J mice and mice with constitutive deletion of ether mu- or delta-opioid receptors (MOR or DOR knockout [KO], respectively). Locomotor activity was assessed in these same animals.Basal locomotor activity of DOR KO was elevated relative to MOR KO, but did not differ from that of WT mice. DOR mice, but not WT or MOR KO, exhibited a significant increase in activity in response to an injection of saline. The acute administration of cocaine produced a dose-related increase in locomotor activity in the three genotypes. The locomotor activating effects of a low dose (10 mg/kg) of cocaine were enhanced in DOR KO mice whereas the locomotor activating effects of both a low and higher (20 mg/kg) dose of cocaine were reduced in MOR KO animals.Microdialysis studies revealed no difference between genotypes in basal DA levels. Acute administration of cocaine, but not saline, increased DA levels in WT and KO animals. Paradoxically, however, the magnitude of this effect was smaller in DOR KO as compared with that in either WT or MOR KO.These data indicate that constitutive deletion of either MOR or DOR results in contrasting effects upon responsiveness to cocaine, which is consistent with the distinct phenotypes previously described for these mutants. Published by Elsevier Ltd on behalf of IBRO.