Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus
Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus
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DOI：
10.1111/j.1460-9568.2005.04401.x
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发表时间：
2005-11-01
影响因子：
3.4
通讯作者：
Lupica, CR
中科院分区：
文献类型：
--
作者：
Hoffman, AF;Macgill, AM;Lupica, CR
在缺乏CB1受体(CB1(-/-))的小鼠中，大麻素受体激动剂WIN55,212-2对谷氨酸能EPSP的持续抑制被定义为一种新的非CB1大麻受体(Hajos等人，2001年)。这种新的受体与CB1的区别还在于它对拮抗剂SR141716A的敏感性和对拮抗剂AM251的不敏感性(Hajos&Freund，2002)。我们选择将这种假定的受体称为CBSC，因为它在海马区的Schaffer侧支轴突终末上被发现。我们研究了SpragueDawley(SD)大鼠和两个野生型(WT)小鼠品系(C57BL/6J和CD1)的CBSC受体的特性，并将其用作两个独立的CB1(-/-)小鼠的背景(Ledent等人，1999；Zimmer等人，1999)。WIN55、212-2在WT CD1小鼠和SD大鼠的海马片上观察到对突触谷氨酸释放的抑制作用，而在WT C57小鼠则无此作用。我们还发现AM251和SR141716A在CD1小鼠和SD大鼠的海马片上拮抗WIN55,212-2的作用，表明这些配体在这些动物中缺乏对CB1和CBSC受体的选择性。结果表明，在CD1小鼠和SD大鼠的海马区存在谷氨酸调节的CBSC大麻素受体，而在C57BL/6J小鼠的海马区则不存在。因此，我们已经确定了可以独立于新的CBSC受体(C57(CB1+/+))、CBSC受体独立于克隆的CB1受体(CD1(CB1-/-))或在两个受体都不存在的情况下(C57(CB1-/-))进行大麻类药物研究的动物模型。
A novel, non-CB1 cannabinoid receptor has been defined by the persistence of inhibition of glutamatergic EPSPs by the cannabinoid receptor agonist WIN55,212-2 in mice lacking the cloned CB1 receptor (CB1(-/-)) (Hajos et al., 2001). This novel receptor was also distinguished from CB1 by its sensitivity to the antagonist SR141716A and its insensitivity to the antagonist AM251 (Hajos & Freund, 2002). We have chosen to refer to this putative receptor as CBsc due to its identification on Schaffer collateral axon terminals in the hippocampus. We examined properties of CBsc receptors in Sprague Dawley (SD) rats and two strains of wild-type (WT) mice (C57BL/6J and CD1) used as backgrounds for two independent lines of CB1(-/-) mice (Ledent et al., 1999; Zimmer et al., 1999). The inhibition of synaptic glutamate release by WIN55,212-2 was observed in hippocampal slices from WT CD1 mice and SD rats but was absent in WT C57 mice. We also found that AM251 and SR141716A antagonized the effect of WIN55,212-2 in hippocampal slices from CD1 mice and SD rats demonstrating a lack of selectivity of these ligands for CB1 and CBsc receptors in these animals. The results indicate that the glutamate-modulating CBsc cannabinoid receptor is present in the hippocampi of CD1 mice and SD rats but not in C57BL/6J mice. Thus, we have identified animal models that may permit the study of cannabinoids independently of the novel CBsc receptor (C57(CB1+/+)), the CBsc receptor independently of the cloned CB1 receptor (CD1(CB1-/-)), or in the absence of both receptors (C57(CB1-/-)).