TIME DEPENDENT EFFECTS OF ETHANOL ON CEREBRAL METABOLISM

乙醇的作用是双相的，与给药时间有关。正强化发生在血液乙醇水平上升的早期。当这些水平下降时，厌恶和厌恶的属性占主导地位。这种时间依赖性支持乙醇在CNS中的作用的多相观点，其中乙醇在乙醇给药后作为时间的函数在独立的脑系统内具有不同的作用。寻求乙醇诱导的不同的神经系统的变化作为时间的函数的证据，本建议将确定乙醇是否会影响不同的神经基板在不同的时间后，乙醇管理，以及这些系统是否适应慢性乙醇暴露在不同的速度。脑图谱研究在这方面具有独特的地位，因为它们同时确定整个大脑的活动水平。该实验室最近表明，乙醇对大鼠大脑功能活动的影响也是时间依赖性的。在一组结构中乙醇给药后立即改变活性，并且随着血液乙醇水平下降，在完全不同的一组结构中改变活性。因此，当浓度上升和下降时，不同的神经回路似乎有助于乙醇的影响。拟议的研究将首先将我们以前在单次剂量下获得的结果扩展到相关剂量范围，以确定这两种脑能量代谢模式发生的剂量和时间条件。我们还提出了初步的数据表明，功能活动适应不同的慢性乙醇在不同的大脑结构的大鼠。因此，目前的研究也将确定如何区域神经活动沿着上升和下降阶段的血液乙醇曲线的变化，以响应慢性暴露于乙醇。这些发现将有助于支持耐受性概念的工作，该概念认识到各种神经回路之间的综合活动是乙醇的时间依赖性效应的原因。

The effects of ethanol are biphasic with respect to administration time. Positive reinforcement occurs early as blood ethanol levels rise. As these levels fall, the depressant and aversive properties predominate. This time-dependency supports a multi-phasic view of ethanol's effects in the CNS in which ethanol has distinct actions within independent brain systems as a function of time after ethanol administration. Seeking evidence of ethanol-induced changes in disparate neural systems as a function of time, the present proposal will determine whether ethanol affects different neural substrates at different times after ethanol administration and whether these systems adapt to chronic ethanol exposure at different rates. Brain mapping studies are in a unique position to contribute significantly in this regard because they determine levels of activity throughout the brain simultaneously. This laboratory has recently shown that ethanol's effects on functional brain activity in the rat are also time-dependent. Activity was altered immediately after ethanol administration in one set of structures, and activity was altered in a completely different set of structures as blood ethanol levels fell. Therefore, it appears that different neural circuits subserve the effects of ethanol when concentrations are rising and falling. The proposed studies will first extend our previous findings obtained at a single dose to a range of relevant doses in order to establish the conditions of dose and time under which each of these two patterns of brain energy metabolism occur. We also present preliminary data which suggest that functional activity adapts differently to chronic ethanol in distinct sets of brain structures in the rat. Therefore, the present studies will also determine how regional neural activity along the rising and falling phases of the blood ethanol curve change in response to chronic exposure to ethanol. These finding swill contribute to the body of work that supports a concept of tolerance which recognizes that integrated activity among various neural circuits are responsible for the time-dependent effects of ethanol.