Mediation of Amphetamine-Induced Long-Term Depression of Synaptic Transmission by CB1 Cannabinoid Receptors in the Rat Amygdala
Mediation of Amphetamine-Induced Long-Term Depression of Synaptic Transmission by CB1 Cannabinoid Receptors in the Rat Amygdala
复制标题
CB1 大麻素受体介导安非他明诱导的大鼠杏仁核突触传递的长期抑制
DOI：
10.1523/jneurosci.23-32-10311.2003
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
P. Gean
中科院分区：
文献类型：
--
作者：
Ya;Su;L. Chiou;P. Gean
杏仁核被认为介导安非他明诱导的条件性位置偏爱的记忆巩固，这是一种行为范式，需要记忆环境线索和药物治疗产生的情感状态之间的关联。在这里，我们表明，安非他明诱导长期突触抑制（LTD）在杏仁核。安非他明LTD不受多巴胺、5-羟色胺1A和去甲肾上腺素α2受体拮抗剂的影响，但可被大麻素CB 1受体拮抗剂AM 251阻断。它被CB 1激动剂WIN 55212 -2模拟，并被内源性大麻素摄取抑制剂AM404促进和部分封闭。安非他明和WIN 55212 -2 LTDs都与成对脉冲易化率的增加和频率的降低有关，但与微型EPSC的振幅无关。它们对P/Q型钙通道阻滞剂的阻断也很敏感，并相互阻断，表明这两种形式的突触可塑性具有共同的潜在机制。用钙螯合剂加载突触后神经元在一些但不是所有测试的神经元中阻断了苯丙胺LTD。然而，在AM404的存在下，安非他明LTD存在于记录的所有神经元中。这些结果表明，安非他明诱导的内源性大麻素释放依赖于细胞内钙离子的上升和LTD在一些神经元中的不完全阻断可能是由于附近细胞的内源性大麻素溢出。内源性大麻素是安非他明的突触作用的基础，这一发现可能为治疗精神兴奋剂成瘾开辟一条新的途径。
The amygdala is thought to mediate memory consolidation of amphetamine-induced conditioned place preference, a behavioral paradigm that requires memory for an association between environmental cues and the affective state produced by the drug treatment. Here we show that amphetamine induces long-term synaptic depression (LTD) in the amygdala. Amphetamine LTD is not affected by dopamine, serotonin 1A, and norepinephrine α2 receptor antagonists but is blocked by the cannabinoid CB1 receptor antagonist AM251. It is mimicked by the CB1 agonist WIN55212-2 and facilitated and partially occluded by endocannabinoid uptake inhibitor AM404. Both amphetamine and WIN55212-2 LTDs are associated with an increase in the ratio of paired-pulse facilitation and a decrease in the frequency but not the amplitude of miniature EPSCs. They are also sensitive to block by P/Q type calcium channel blocker and occluded by each other, indicating that these two forms of synaptic plasticity share a common underlying mechanism. Loading postsynaptic neuron with calcium chelator blocked amphetamine LTD in some but not all neurons tested. However, in the presence of AM404, amphetamine LTD was present in all neurons recorded. These results suggest that amphetamine-induced endocannabinoid release depends on a rise in intracellular calcium and the incomplete block of LTD in some neurons may be attributable to the spillover of endocannabinoid from nearby cells. The finding that endocannabinoids underlie the synaptic actions of amphetamine may open a new avenue for the treatment of psychostimulants addiction.
anandamide 转运蛋白识别和易位的结构决定因素。
DOI：
10.1073/pnas.96.10.5802
发表时间：
1999
影响因子：
11.1
作者：
Piomelli,D;Beltramo,M;Glasnapp,S;Lin,SY;Goutopoulos,A;Xie,XQ;Makriyannis,A
通讯作者：
Makriyannis,A