Activation of the cannabinoid receptor type 1 decreases glutamatergic and GABAergic synaptic transmission in the lateral amygdala of the mouse
Activation of the cannabinoid receptor type 1 decreases glutamatergic and GABAergic synaptic transmission in the lateral amygdala of the mouse
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DOI：
10.1101/lm.53303
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发表时间：
2003-03-01
影响因子：
2
通讯作者：
Rammes, G
中科院分区：
文献类型：
--
作者：
Azad, SC;Eder, M;Rammes, G
内源性大麻素系统最近被证明在消除厌恶记忆中起着至关重要的作用。由于杏仁核可能参与了这一过程，我们研究了大麻素受体激动剂WIN 55,212-2 （WIN-2）对野生型和大麻素受体1型（CB1）缺陷小鼠侧杏仁核（TA）突触传递的影响。在体外切片制备中进行细胞外场电位记录和膜片钳实验。我们发现WIN-2在野生型小鼠中减少了基础突触传递和药理学分离的AMPA受体和GABA(A)受体介导的突触后电流，但在cbi缺陷小鼠中没有。这些结果表明，在LA中，大麻素通过CB1调节兴奋性和抑制性突触传递。win -2诱导的成对脉冲比以及自发和微型突触后电流的变化表明突触前有作用。抑制蛋白和阻断电压依赖性和G蛋白门控的内向纠偏K+通道可抑制WIN-2在基础突触传递中的作用。相比之下，腺苷酸环化酶-蛋白激酶A途径的调节，突触前N-和P/Q-或突触后L-和R/ t型电压门控Ca2+通道的阻断并不影响WIN-2的作用。我们的研究结果表明，大麻素在LA中的作用机制部分类似于在伏隔核中观察到的机制，而在海马中所描述的机制有所不同。
The endogenous cannabinoid system has been shown recently to play a crucial role in the extinction of aversive memories. As the amygdala is presumably involved in this process, we investigated the effects of the cannabinoid receptor agonist WIN 55,212-2 (WIN-2) on synaptic transmission in the lateral amygdala (TA) of Wild-type and cannabinoid receptor type 1 (CB1)-deficient mice. Extracellular field potential recordings and patch-clamp experiments were performed in an in vitro slice preparation. We found that WIN-2 reduces basal synaptic transmission and pharmacologically isolated AMPA receptor- and GABA(A) receptor-mediated postsynaptic currents in wild-type, but not in CBI-deficient mice. These results indicate that, in the LA, cannabinoids modulate both excitatory and inhibitory synaptic transmission via CB1. WIN-2-induced changes of paired-pulse ratio and of spontaneous and Miniature postsynaptic currents suggest a presynaptic site of action. Inhibition of proteins and blockade of voltage-dependent and G protein-gated inwardly rectifying K+ channels inhibited WIN-2 action on basal synaptic transmission. In contrast, modulation of the adenylyl cyclase-protein kinase A pathway, and blockade of presynaptic N- and P/Q- or of postsynaptic L- and R/T-type voltage-gated Ca2+ channels did not affect WIN-2 effects. Our results indicate that the mechanisms underlying cannabinoid action in the LA partly resemble those observed in the nucleus accumbens and differ front those described for the hippocampus.