Noradrenaline triggers GABAA inhibition of bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area
Noradrenaline triggers GABAA inhibition of bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area
复制标题
DOI：
10.1523/jneurosci.0425-04.2004
复制
发表时间：
2004-09-22
影响因子：
5.3
通讯作者：
Williams, JT
中科院分区：
文献类型：
--
作者：
Dumont, ÉC;Williams, JT
终纹腹侧床核（vlBNST）的外侧部分是阿片类药物戒断期间去甲肾上腺素能药物抗厌恶作用的关键部位。本研究的目的是确定去甲肾上腺素在 5 天吗啡治疗停药后对 vlBNST 的细胞作用。 vlBNST 是具有多个传出投射的异质细胞群。因此，通过注射到腹侧被盖区（VTA）的荧光微球的逆行运输来识别投射到中脑的神经元。这些神经元和那些具有共同生理特性的神经元的全细胞电压钳记录是在脑切片中完成的。去甲肾上腺素激活 α(1)-肾上腺素能受体以增加 GABA(A)-IPSC 频率。去甲肾上腺素在急性阿片类药物戒断期间使 GABA(A)-IPSC 产生类似的增加，但这种增加是由于 β-肾上腺素能受体、腺苷酸环化酶和蛋白激酶 A 以及 α(1)-肾上腺素能受体的激活所致。鉴于 vlBNST 中的神经元向 VTA 发送兴奋性投射，去甲肾上腺素可能会减少中脑边缘多巴胺细胞的兴奋性驱动。这种机制可能有助于戒断诱导的多巴胺神经元抑制，并解释微量注射到 vlBNST 中的去甲肾上腺素能药物如何减少阿片类药物戒断的厌恶情绪。
The lateral part of the ventral bed nucleus of the stria terminalis (vlBNST) is a critical site for the antiaversive effects of noradrenergic drugs during opioid withdrawal. The objective of the present study is to identify the cellular action(s) of noradrenaline in the vlBNST after withdrawal from a 5 d treatment with morphine. The vlBNST is a heterogeneous cell group with multiple efferent projections. Therefore, neurons projecting to the midbrain were identified by retrograde transport of fluorescent microspheres injected in the ventral tegmental area (VTA). Whole-cell voltage clamp recordings of these neurons and of those sharing physiological properties were done in brain slices. Noradrenaline activated alpha(1)-adrenergic receptors to increase GABA(A)-IPSC frequency. Noradrenaline produced a similar increase in GABA(A)-IPSCs during acute opioid withdrawal, but this increase resulted from activation of beta-adrenergic receptors, adenylyl cyclase, and protein kinase A, as well as alpha(1)-adrenergic receptors. Given that neurons in the vlBNST send an excitatory projection to the VTA, noradrenaline may reduce excitatory drive to mesolimbic dopamine cells. This mechanism might contribute to the withdrawal-induced inhibition of dopamine neurons and explain how noradrenergic drugs microinjected into the vlBNST reduce aversive aspects of opioid withdrawal.