Berridge C W, Wifler K
Psychology Department, University of Wisconsin, Madison, WI 53706-1611, USA.
Neuroscience. 2000;97(3):543-52. doi: 10.1016/s0306-4522(00)00047-6.
The locus coeruleus-noradrenergic system participates in the modulation of behavioral state. Previous studies demonstrated that beta-receptors located within the general region encompassing the medial septum/vertical limb of the diagonal band of Broca (medial septal area) exert arousal-enhancing actions in both anesthetized and unanesthetized animals. These studies also demonstrated that, under conditions of limited locus coeruleus discharge rates, blockade of beta-receptors within this region decreased forebrain electroencephalographic indices of arousal. The current studies assess the extent to which medial septal area beta-receptors contribute to the maintenance of electroencephalographic and/or behavioral indices of arousal, under conditions associated with elevated locus coeruleus discharge rates. In the halothane-anesthetized rat, bilateral, but not unilateral, blockade of beta-receptors within this area prevented forebrain (cortical and hippocampal) electroencephalographic activation elicited by activation of locus coeruleus neurons. Placement of beta-antagonist immediately adjacent to the medial septal area had no effect on locus coeruleus-dependent cortical and hippocampal electroencephalographic activation. In contrast, in unanesthetized rat, bilateral pretreatment of the medial septal area did not alter either electroencephalographic or behavioral measures in animals tested in an arousal-enhancing, brightly-lit novel environment, which has been demonstrated to elicit an activation of the locus coeruleus-noradrenergic system. The results obtained in anesthetized animals are consistent with previous studies demonstrating potent modulatory actions of noradrenergic systems on actions of general anesthetics, and suggest that beta-receptors may be an appropriate target for pharmacological adjuncts to general anesthetics. In contrast to that observed in anesthetized animals, medial septal beta-receptors alone do not contribute significantly to the maintenance of an activated forebrain in unanesthetized animals. It is presumed that actions of other noradrenergic receptors and/or other neurotransmitter systems located within or outside the medial septal area make the arousal-modulating actions of medial septal area beta-receptors redundant, in the unanesthetized, alert animal.
蓝斑-去甲肾上腺素能系统参与行为状态的调节。先前的研究表明，位于包括内侧隔区/布罗卡斜带垂直支（内侧隔区）在内的一般区域内的β受体，在麻醉和未麻醉的动物中均发挥增强觉醒的作用。这些研究还表明，在蓝斑放电率有限的情况下，该区域内β受体的阻断会降低前脑脑电图的觉醒指标。当前的研究评估了在内侧隔区β受体在蓝斑放电率升高的情况下，对维持脑电图和/或行为觉醒指标的贡献程度。在氟烷麻醉的大鼠中，该区域内β受体的双侧而非单侧阻断可防止蓝斑神经元激活所引发的前脑（皮质和海马）脑电图激活。将β拮抗剂紧邻内侧隔区放置，对蓝斑依赖性皮质和海马脑电图激活无影响。相比之下，在未麻醉的大鼠中，内侧隔区的双侧预处理并未改变在增强觉醒的明亮新奇环境中测试的动物的脑电图或行为指标，该环境已被证明可引发蓝斑-去甲肾上腺素能系统的激活。在麻醉动物中获得的结果与先前的研究一致，这些研究表明去甲肾上腺素能系统对全身麻醉药的作用具有强大的调节作用，并表明β受体可能是全身麻醉药药理学辅助剂的合适靶点。与在麻醉动物中观察到的情况相反，内侧隔区的β受体单独对未麻醉动物中激活的前脑的维持没有显著贡献。据推测，在内侧隔区内或外的其他去甲肾上腺素能受体和/或其他神经递质系统的作用，使得内侧隔区β受体在未麻醉、警觉的动物中的觉醒调节作用变得多余。
