ANTIDEPRESSANTS AND MONOAMINE RECEPTORS AND RESPONSES

这项研究的目的是更好地了解 抗抑郁药给药后的药理效应 时间，关于中枢生物胺神经元系统。预计这将是 导致对情感性疾病生物学的更好理解 以改善这些疾病的治疗。特别是，我们打算研究 慢性治疗大鼠是否具有多种已有和较新的 抗抑郁治疗导致β-肾上腺素能受体的发展 不敏感。β肾上腺素能受体的研究将使用 放射性β-肾上腺素能拮抗剂(负)~3H-二氢肾上腺素(~3H-DHA)。在……里面 此外，计划进行的实验应该会提供一些关于 抗抑郁药物诱导中枢神经系统发育的临床意义 β-肾上腺素能受体亚敏感。这种类型的扩展 调查将我们使用~3H-5羟色胺(5-羟色胺)来标记 中枢性5-羟色胺能受体从而探讨反复作用的影响 用不同类型的精神药物治疗大鼠对这些受体的影响。 松果体将被用来测量抗抑郁治疗的效果 在体内和体外的肾上腺素能反应性。儿茶酚胺将是 外源性给药给急性或慢性用药的大鼠 抗抑郁药物与3‘，5’-单磷酸腺苷的浓度 (环磷酸腺苷)在松果体测量。此外，急性脑损伤的能力 并用去甲基米帕明慢性治疗大鼠来调节肾上腺素能 内源性释放去甲肾上腺素引起的松果体反应 我们将对支配松果体的交感神经进行研究。

The goal of this research is to provide a better understanding of the pharmacological effects of antidepressant treatments, when administered over time, on central biogenic amine neuronal systems. This would be expected to lead to an improved understanding of the biology of affective illnesses and toward improved treatment of these illnesses. In particular, we intend to study whether chronic treatment of rats with a variety of established and newer antidepressant treatments causes the development of beta-adrenergic receptor subsensitivity. Beta-adrenergic receptors will be studied with the use of the radioactive beta-adrenergic antagonist (minus)3H-dihydroalrenolol (3H-DHA). In addition, experiments are planned that should provide some information on the clinical relevance of the antidepressant drug-induced development of central beta-adrenergic receptor subsensitivity. An expansion of this type of investigation will be our use of 3H-5hydroxytryptamine (serotonin) to label central serotonergic receptors so as to investigate the effects of repeated treatment of rats with different types of psychotropic drugs on these receptors. The pineal gland will be used to measure the effect of antidepressant treatments on adrenergic responsiveness both in vivo and in vitro. Catecholamines will be administered exogenously to rats treated either acutely or chronically with antidepressant drugs and the concentration of adenosine 3',5' monophosphate (cyclic AMP) in the pineal gland measured. In addition, the ability of acute and chronic treatment of rats with desmethylimipramine to modify adrenergic responses in the pineal gland caused by norepinephrine released endogenously from the sympathetic nerve innervating the pineal gland will be studied.