ANTIDEPRESSANTS AND MONOAMINE RECEPTORS AND RESPONSES

本项目的目标是确定：（1）如果不同类型 抗抑郁药的使用改变了亚型的密度和/或亲和力 β肾上腺素能受体（BAR）或5-HT-1受体， 整个大脑或局部区域;（2）神经递质如何 神经改变抗抑郁药降低密度的能力 （3）影响BARs调控的因素 体内;和（4）如果某些中枢受体发生变化， 单胺出现在抑郁症的动物模型中。 所有实验 将使用大鼠和受体将可视化和定量使用 体外定量放射自显影技术。 许多 抗抑郁药降低BAR的密度， 药理学作用被推测与其 临床效果 所提出的实验将评估 BAR的特定亚型优先受到以下因素的影响： 抗抑郁药以及是否在共同区域产生变化 大脑。 除了影响去甲肾上腺素能 反应性，抗抑郁药改变电生理 和5-羟色胺（5-HT）激动剂引起的行为反应。 的 改变的反应与一种受体的亚型有关， 5-HT，称为5-HT-1受体。 通过使用定量 放射自显影，将有可能确定 抗抑郁药诱导的这些亚型的变化解释了 反应的改变。 在实验中， BAR或5-HT-1受体亚型，将给予大鼠 不同类型的抗抑郁药21天。 抗抑郁 研究将是那些选择性地阻止吸收 去甲肾上腺素或血清素或选择性抑制A型或 B单胺氧化酶。 血清素神经元参与了 抗抑郁药诱导的BAR密度降低。 研究 这种抗抑郁药地昔帕明或 β-激动剂异丙肾上腺素（ISO），以降低BAR的密度 将在完整大鼠或中枢神经系统损伤大鼠中测量 肾上腺素能神经元。 会用神经毒素造成损伤， 5，7-二羟色胺，不仅脑室给药， 直接进入含有去甲肾上腺素能细胞体或神经的区域 terminals. 儿茶酚胺能神经的神经毒素损伤， 将在单独的大鼠组中制备6-羟基多巴胺， 确定中枢去甲肾上腺素能神经元如何影响 降低β 1肾上腺素能受体的密度。 在这些 实验中，将ISO注入右侧脑室， 大鼠通过连接到Alzet的永久留置套管 微型泵 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。 地位 还将在大鼠中测量PF中枢单胺受体 暴露于不受控制的休克，因为这可能是一种动物模型， 萧条

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.