ANTIDEPRESSANTS AND MONOAMINE RECEPTORS AND RESPONSES

该项目的目标是确定：(1)不同类型的 抗抑郁药改变了亚型的密度和/或亲和力 β肾上腺素能受体(BAR)或5-羟色胺-1受体 整个大脑或局部区域；(2)5-羟色胺 神经改变抗抑郁药物降低密度的能力 关于酒吧；(3)涉及中央酒吧监管的因素 活体；以及(4)如果某些中枢受体的变化 单胺类物质存在于抑郁症的动物模型中。所有实验 将使用大鼠和受体将被可视化和量化使用 体外定量放射自显影技术。许多 抗抑郁药降低了酒吧的密度，这 据推测，药理作用与它们的 临床效果。拟议中的实验将评估一个 条形的特定子类型优先受 抗抑郁药以及是否在公共区域产生变化 大脑的一部分。除了影响去甲肾上腺素 反应性，抗抑郁药改变了两种电生理 5-羟色胺(5-羟色胺)激动剂引起的行为反应。这个 改变的反应与一种受体的亚型有关 5-羟色胺，称为5-羟色胺-1受体。通过使用量化 放射自显影，就有可能确定 抗抑郁药引起的这些亚型的变化解释了 响应性的变化。在涉及到的实验中 BAR或5-HT-1受体亚型，大鼠将被给予 不同类型的抗抑郁药，疗程21天。抗抑郁药 研究对象将是那些选择性地阻止吸收 去甲肾上腺素或5-羟色胺或选择性抑制A型或A型 B单胺氧化酶。5-羟色胺神经元参与了 抗抑郁剂导致的酒吧密度下降。学习 这一点，无论是抗抑郁剂地昔帕明，还是 β-激动剂异丙肾上腺素(ISO)，以降低条密度 将在完整的大鼠或中枢神经损伤的大鼠身上进行测量 5-羟色胺能神经元损伤将与神经毒素一起造成， 5，7-二羟色胺，不仅脑室注射，而且 直接进入含有去甲肾上腺素胞体或神经的区域 终点站。神经毒素对儿茶酚胺能神经的损伤， 6-羟基多巴胺，将在不同的大鼠组中制造 确定中枢去甲肾上腺素能神经元如何影响这种能力 降低β-1肾上腺素能受体密度。在这些 实验中，将ISO注入右侧脑室 通过与阿尔茨海默病相连的永久留置套管 迷你车。本实验将提供有关 使用β-受体激动剂作为抗抑郁药的可行性。该状态 还将在大鼠身上测量Pf中枢单胺受体 暴露在失控的休克中，因为这可能是一种 抑郁症。

The goals of this project are to determine: (1) if different types of antidepressants alter the density and/or affinity of subtypes of either beta adrenoceptors (BARs) or 5-HT-1 receptors either throughout the brain or in localized areas; (2) how serotonergic nerves alter the ability of antidepressants to decrease the density of BARs; (3) factors involved in the regulation of central BARs in vivo; and (4) if alterations in central receptors for certain monamines occur in an animal model of depression. All experiments will use rats and receptors will be visualized and quantified using the technique of in vitro quantitative autoradiography. Many antidepressants decrease the density of BARs and this pharmacological effect has been speculated to be involved in their clinical effects. The experiments proposed will evaluate if a particular subtype of BAR is preferentially affected by antidepressants and whether changes are produced in common areas of the brain. In addition to affecting noradrenegic responsiveness, antidepressants change both electrophysiological and behavior responses elicited by serotonin (5-HT) agonists. The responses altered have been linked to subtypes of a receptor for 5-HT, termed the 5-HT-1 receptor. By using quantitative autoradiography, it will be possible to determine whether antidepressant-induced changes in these subtypes account for the alterations in responsiveness. In the experiments involving subtypes of BARs or 5-HT-1 receptors, rats will be given antidepressant of different types for 21 days. Antidepressants studied will be those that block selectively the uptake of norepinephrine or serotonin or inhibit selectively type A or type B monoamine oxidase. Serotonin neurons are involved in antidepressant-induced decreases in the density of BARs. To study this, the ability of either the antidepressant, desipramine, or the beta-agonist, isoproterenol (ISO), to decrease the density of BARs will be measured in intact rats or rats with lesions of central serotonergic neurons. Lesions will be made with the neurotoxin, 5,7-dihydroxytryptamine, given not only intraventricularly but also directly into areas containing noradrenegic cell bodies or nerve terminals. Lesions with a neurotoxin for catecholaminergic nerves, 6-hydroxydopamine, will be made in separate groups of rats to determine how central noradrenegic neurons influence the ability of ISO to decrease the density of beta-1 adrenoceptors. In these experiments, ISO will be given into the right lateral ventricle of rats through a permanently indwelling cannula connected to an Alzet minipump. This experiment will provide information about the feasibility of using beta agonists as antidepressants. The status pf central monoamine receptors will also be measured in rats exposed to uncontrolled shock, as this may be an animal model of depression.