Receptor subtype-dependent galanin actions on gamma-aminobutyric acidergic neurotransmission and ethanol responses in the central amygdala.

Receptor subtype-dependent galanin actions on gamma-aminobutyric acidergic neurotransmission and ethanol responses in the central amygdala.
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DOI:
10.1111/j.1369-1600.2011.00360.x
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发表时间:
2012-07
期刊:
影响因子:
3.4
通讯作者:
Siggins GR
Siggins GR
中科院分区:
医学2区
文献类型:
--
作者:
Bajo M;Madamba SG;Lu X;Sharkey LM;Bartfai T;Siggins GR

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神经肽甘丙肽及其三种受体亚型(GalR 1 -3)在中央杏仁核(CeA)中表达,这是一个涉及压力和焦虑相关行为以及酒精依赖的大脑区域。甘丙肽也被认为在酒精摄入和酒精依赖中发挥作用。我们研究了甘丙肽在来自GalR 2和GalR 1和GalR 2受体缺陷的野生型(WT)和敲除(KO)小鼠的CeA切片中的作用。甘丙肽对GABA能的传递有双重作用,在超过一半的CeA神经元中,降低药理学分离的GABA能抑制性突触后电位(IPSPs)的幅度,但在其他神经元中增加IPSPs。GalR 3拮抗剂SNAP 37889灌流后IPSP大小不增加,而GalR 1 × GalR 2双KO和GalR 2 KO小鼠的CeA神经元中不存在IPSP抑制。成对脉冲易化研究表明,甘丙肽对GABA释放的影响很弱或很少。因此,甘丙肽可能通过GalR 3在突触后起作用,以增加某些CeA神经元中的GABA能传递,而GalR 2受体可能参与IPSP的抑制。共灌流的乙醇,增强突触前IPSPs,与甘丙肽一起引起的乙醇和甘丙肽在这些CeA神经元显示甘丙肽增强IPSPs的总和效应,这表明这两种药物通过不同的机制在这个群体中发挥作用。然而,在显示IPSP减少甘丙肽效应的神经元中,甘丙肽减弱了乙醇的效应,表明甘丙肽的抢先效应。这些发现可能会增加理解的复杂的细胞机制的焦虑相关的行为影响的甘丙肽和乙醇在CeA。
The neuropeptide galanin and its three receptor subtypes (GalR1–3) are expressed in the central amygdala (CeA), a brain region involved in stress- and anxiety-related behaviors, as well as alcohol dependence. Galanin also has been suggested to play a role in alcohol intake and alcohol dependence. We examined the effects of galanin in CeA slices from wild type (WT) and knockout (KO) mice deficient of GalR2 and both GalR1 and GalR2 receptors. Galanin had dual effects on GABAergic transmission, decreasing the amplitudes of pharmacologically-isolated GABAergic inhibitory postsynaptic potentials (IPSPs) in over half of CeA neurons but augmenting IPSPs in the others. The increase in IPSP size was absent after superfusion of the GalR3 antagonist SNAP 37889, whereas the IPSP depression was absent in CeA neurons of GalR1 × GalR2 double KO and GalR2 KO mice. Paired-pulse facilitation studies showed weak or infrequent effects of galanin on GABA release. Thus, galanin may act postsynaptically through GalR3 to augment GABAergic transmission in some CeA neurons, whereas GalR2 receptors likely are involved in the depression of IPSPs. Co-superfusion of ethanol, which augments IPSPs presynaptically, together with galanin caused summated effects of ethanol and galanin in those CeA neurons showing galanin-augmented IPSPs, suggesting the two agents act via different mechanisms in this population. However, in neurons showing IPSP-diminishing galanin effects, galanin blunted the ethanol effects, suggesting a preemptive effect of galanin. These findings may increase understanding of the complex cellular mechanisms that underlie the anxiety-related behavioral effects of galanin and ethanol in CeA.
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