Morrisett R A, Swartzwelder H S
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260.
J Neurosci. 1993 May;13(5):2264-72. doi: 10.1523/JNEUROSCI.13-05-02264.1993.
Long-term potentiation of synpatic transmission (LTP) of the perforant path--dentate gyrus synapse is induced by 5 Hz, theta-like stimulation patterns. Such stimuli induce plasticity that is most likely driven by a decrease in synaptic inhibition (disinhibition) mediated by GABAB autoreceptors. In the present study, we demonstrate that LTP induced in this manner is completely antagonized by ethanol. In order to determine the site of ethanol inhibition of LTP induced by theta-like stimulation, we combined slice patch recordings with pharmacologic isolation of the individual glutamatergic and GABAergic synaptic currents. The present experiments revealed that ethanol inhibited NMDA receptor-mediated synaptic currents without potentiation of GABAA currents or attenuation of GABAB-mediated fading of GABAA synaptic currents. These observations with ethanol contrasted with the actions of the water-soluble benzodiazepine midazolam, which strongly potentiated GABAA synaptic currents, reversed the effect of GABAB-mediated fading of GABAA synaptic currents, and therefore blocked the resulting NMDA synaptic currents. These data indicate that the effects of ethanol on long-term changes in synaptic strength in the rat hippocampal formation are due primarily to an action at the NMDA receptor-channel complex.
穿通通路-齿状回突触的突触传递长时程增强（LTP）由5 Hz、类θ刺激模式诱导产生。此类刺激诱导的可塑性很可能是由GABAB自身受体介导的突触抑制（去抑制）减弱所驱动。在本研究中，我们证明以这种方式诱导的LTP完全被乙醇拮抗。为了确定乙醇抑制类θ刺激诱导的LTP的位点，我们将脑片膜片钳记录与对单个谷氨酸能和GABA能突触电流的药理学分离相结合。本实验表明，乙醇抑制NMDA受体介导的突触电流，而不增强GABAA电流或减弱GABAB介导的GABAA突触电流的衰减。乙醇的这些观察结果与水溶性苯二氮䓬类药物咪达唑仑的作用形成对比，咪达唑仑强烈增强GABAA突触电流，逆转GABAB介导的GABAA突触电流衰减的效应，从而阻断由此产生的NMDA突触电流。这些数据表明，乙醇对大鼠海马结构突触强度长期变化的影响主要是由于其作用于NMDA受体-通道复合体。
