Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
J Neurosci. 2012 May 2;32(18):6072-80. doi: 10.1523/JNEUROSCI.6486-11.2012.
The presynaptic source of dopamine in the CA1 field of dorsal hippocampus is uncertain due to an anatomical mismatch between dopaminergic terminals and receptors. We show, in an in vitro slice preparation from C57BL/6 male mice, that a dopamine (DA) D1 receptor (D1R)-mediated enhancement in glutamate synaptic transmission occurs following release of endogenous DA with amphetamine exposure. It is assumed DA is released from terminals innervating from the ventral tegmental area (VTA) even though DA transporter (DAT)-positive fibers are absent in hippocampus, a region with abundant D1Rs. It has been suggested this results from a lack of DAT expression on VTA terminals rather than a lack of these terminals per se. Neither a knockdown of tyrosine hydroxylase (TH) expression in the VTA by THsiRNA, delivered locally, by adeno-associated viral vector, nor localized pharmacological blockade of DAT to prevent amphetamine uptake into DA terminals, has any effect on the D1R synaptic, enhancement response to amphetamine. However, either a decrease in TH expression in the locus ceruleus (LC) or a blockade of the norepinephrine (NE) transporter prevents the DA-mediated response, indicating LC terminals can release both NE and DA. These findings suggest noradrenergic fibers may be the primary source of DA release in hippocampus and corresponding DA-mediated increase in synaptic transmission. Accordingly, these data imply the LC may have a role in DA transmission in the CNS in response to drugs of abuse, and potentially, under physiological conditions.
由于背海马 CA1 场的多巴胺能末梢和受体之间存在解剖学不匹配，多巴胺（DA）在该部位的突触前来源尚不确定。我们在来自 C57BL/6 雄性小鼠的体外切片制备中表明，在暴露于安非他命时，内源性 DA 的释放会引起谷氨酸突触传递的多巴胺 D1 受体（D1R）介导的增强。假设 DA 是从支配腹侧被盖区（VTA）的末梢释放的，尽管在富含 D1R 的海马体中不存在 DA 转运体（DAT）阳性纤维。有人认为，这是由于 VTA 末梢缺乏 DAT 表达，而不是这些末梢本身缺乏。通过腺相关病毒载体局部递送电酪氨酸羟化酶（TH）siRNA 降低 VTA 中的 TH 表达，或局部药理学阻断 DAT 以防止安非他命进入 DA 末梢摄取，都不会对 D1R 突触对安非他命的增强反应产生任何影响。然而，无论是降低蓝斑（LC）中的 TH 表达还是阻断去甲肾上腺素（NE）转运体都可以阻止 DA 介导的反应，表明 LC 末梢可以释放 NE 和 DA。这些发现表明，去甲肾上腺素能纤维可能是海马体中 DA 释放的主要来源，并且相应地，DA 介导的突触传递增加。因此，这些数据表明 LC 可能在中枢神经系统对滥用药物的 DA 传递中发挥作用，并且在潜在的生理条件下也可能发挥作用。
