NORADRENERGIC MECHANISMS OF ANTIDEPRESSANT ACTIVITY

研究的重点是阐明去甲肾上腺素能机制 参与抗抑郁活性。研究计划描述了 实验来测试两个假设。首先，假设 β-2肾上腺素能自身受体存在于去甲肾上腺素能末梢上， 中枢神经系统，这些受体参与 介导中枢作用的抗抑郁样行为效应 β肾上腺素能激动剂 其次，假设非典型/β-3 肾上腺素能受体存在于中枢神经系统中， 刺激这些受体产生抗抑郁样作用， 行为这些假设将使用行为和 神经药理学技术拟采用的具体程序 包括检查药物对维持在一个 低速率操作性时间表的差异强化测量 使用受体和腺苷酸环化酶测定的药物-受体相互作用，以及 使用灌流的体外去甲肾上腺素释放的评估 体内使用微透析。第二，相关研究领域， 不是研究计划的正式组成部分，涉及检查 IV型磷酸二酯酶抑制剂的抗抑郁潜力 研究这种酶的活性及其对 药理学抑制由中枢去甲肾上腺素能神经元调节。

The focus of the research is on elucidating noradrenergic mechanisms involved in antidepressant activity. The research plan describes experiments to test two overall hypotheses. First, it is hypothesized that beta-2 adrenergic autoreceptors are present on noradrenergic terminals in the central nervous system and that these receptors are involved in mediating the antidepressant-like behavioral effects of centrally acting beta adrenergic agonists. Second, it is hypothesized that atypical/beta-3 adrenergic receptors are present in the central nervous system and that stimulation of these receptors produces antidepressant-like effects on behavior. These hypotheses will be tested using both behavioral and neuropharmacological techniques. The specific procedures to be employed include examination of drug effects on behavior maintained under a differential-reinforcement-of-low-rate operant schedule, measurement of drug-receptor interactions using receptor and adenylyl cyclase assays, and assessment of norepinephrine release in vitro using superfusion and in vivo using microdialysis. The second, related area of research, which is not a formal component of the research plan, involves the examination of the antidepressant potential of inhibitors of Type IV phosphodiesterase and the study of how the activity of this enzyme and its sensitivity to pharmacological inhibition are regulated by central noradrenergic neurons.