Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425 and Department of Psychology and Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T1Z4.
J Neurosci. 2014 Mar 5;34(10):3706-18. doi: 10.1523/JNEUROSCI.0623-13.2014.
Dopamine (DA) receptors in the medial prefrontal cortex (mPFC) exert powerful effects on cognition by modulating the balance between excitatory and inhibitory neurotransmission. The present study examined the impact of chronic intermittent ethanol (CIE) exposure on cognitive function and DA receptor-mediated neurotransmission in the rat mPFC. Consistent with alterations in executive function in alcoholics, CIE-exposed rats exhibited deficits in behavioral flexibility in an operant set-shifting task. Since alterations in dopaminergic neurotransmission in the mPFC have been implicated in a number of behavioral disorders including addiction, studies were then performed in the adult acute slice preparation to examine changes in DA receptor function in the mPFC following CIE exposure. In slices obtained from control rats, DA receptor stimulation was observed to exert complex actions on neuronal firing and synaptic neurotransmission that were not only dependent upon the particular receptor subtype but also whether it was a pyramidal cell or a fast-spiking interneuron. In contrast to slices from control rats, there was a near complete loss of the modulatory actions of D2/D4 receptors on cell firing and neurotransmission in slices obtained immediately, 1 and 4 weeks after the last day of CIE exposure. This loss did not appear to be associated with changes in receptor expression. In contrast, CIE exposure did not alter D1 receptor function or mGluR1 modulation of firing. These studies are consistent with the suggestion that chronic alcohol exposure disrupts cognitive function at least in part through disruption of D2 and D4 receptor signaling in mPFC.
中前额皮质（mPFC）中的多巴胺（DA）受体通过调节兴奋性和抑制性神经递质之间的平衡，对认知产生强大影响。本研究检查了慢性间歇性乙醇（CIE）暴露对大鼠 mPFC 中认知功能和 DA 受体介导的神经传递的影响。与酒精中毒者执行功能的改变一致，CIE 暴露的大鼠在操作性条件反射转换任务中表现出行为灵活性缺陷。由于 mPFC 中多巴胺能神经传递的改变与包括成瘾在内的许多行为障碍有关，因此随后在成年急性切片制备中进行了研究，以检查 CIE 暴露后 mPFC 中 DA 受体功能的变化。在来自对照大鼠的切片中，观察到 DA 受体刺激对神经元放电和突触神经传递产生复杂作用，这些作用不仅取决于特定的受体亚型，还取决于它是锥体神经元还是快速放电中间神经元。与对照大鼠的切片不同，在 CIE 暴露最后一天后的即刻、1 周和 4 周获得的切片中，D2/D4 受体对细胞放电和神经传递的调节作用几乎完全丧失。这种损失似乎与受体表达的变化无关。相比之下，CIE 暴露并未改变 D1 受体功能或 mGluR1 对放电的调节。这些研究与以下观点一致，即慢性酒精暴露至少部分通过破坏 mPFC 中的 D2 和 D4 受体信号而破坏认知功能。
