STUDIES IN-VIVO ON RELATIONSHIP BETWEEN BRAIN TRYPTOPHAN, BRAIN 5-HT SYNTHESIS AND HYPERACTIVITY IN RATS TREATED WITH A MONOAMINE OXIDASE INHIBITOR AND L-TRYPTOPHAN
STUDIES IN-VIVO ON RELATIONSHIP BETWEEN BRAIN TRYPTOPHAN, BRAIN 5-HT SYNTHESIS AND HYPERACTIVITY IN RATS TREATED WITH A MONOAMINE OXIDASE INHIBITOR AND L-TRYPTOPHAN
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DOI：
10.1111/j.1471-4159.1971.tb12034.x
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发表时间：
1971-01-01
影响因子：
4.7
通讯作者：
GRAHAMESMITH, DG
中科院分区：
文献类型：
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作者：
GRAHAMESMITH, DG
本文研究了l-色氨酸负荷对单胺氧化酶抑制剂处理的大鼠脑内5-羟色胺蓄积量的影响。脑内5-羟色胺的积累量随着色氨酸剂量和脑色氨酸浓度的增加而增加，当色氨酸剂量为120 mg/kg体重时，脑中5-羟色胺的积累量约为70μg/g脑。超过这个剂量和浓度，脑内5-羟色胺的积聚没有进一步增加。在单胺氧化酶抑制和色氨酸负荷后，出现大体亢进和高热。抑制单胺氧化酶、给予色氨酸和完整的芳香氨基酸脱羧酶活性都是产生过度活动和高热的共同必备条件。DL-对氯苯丙氨酸既可预防多动的发生，又可防止脑内5-羟色胺的增加。多动指数与色氨酸负荷后1h脑内5-羟色胺的积累量相关，而与脑内5-羟色胺的总浓度无关，提示多动依赖于5-羟色胺的合成速率。利血平和苯那津预处理加快了多动状态的发生和发展速度，但不改变脑组织5-羟色胺的合成。当单胺氧化酶被抑制，5-羟色胺合成速率增加时，5-羟色胺的颗粒摄取和储存以及其他5-羟色胺失活的限速机制不能阻止5-羟色胺‘溢出’而产生亢进。5-羟色胺合成的关键依赖于脑色氨酸浓度和神经元内代谢的能力，在单胺氧化酶活性保持不变的情况下，为了应对增加的5-羟色胺合成并防止‘溢出’，增加了大脑5-羟色胺合成正常超过功能需要的可能性。提示5-羟色胺池的神经元内代谢和神经元内组织在调节5-羟色胺可用于功能活动的量方面比合成更重要。
The effect ofl‐tryptophan loading upon the amount of 5‐HT accumulating in the brains of rats pretreated with a monoamine oxidase inhibitor was studied. The amount of brain 5‐HT accumulated increased with increasing tryptophan dosages and brain tryptophan concentrations up to a tryptophan dose of 120 mg/kg body wt. and a brain tryptophan of about 70 μg/g brain. Above this dose and concentration no further increase in brain 5‐HT accumulation occurred. After monoamine oxidase inhibition and tryptophan loading gross hyperactivity and hyperpyrexia occurred. Monoamine oxidase inhibition, tryptophan administration and intact aromatic amino acid decarboxylase activity were all collectively essential for the production of hyperactivity and hyperpyrexia. DL‐Parachlorophenyl‐alanine prevented both the occurrence of hyperactivity and the increased accumulation of, brain 5‐HT. Indices of hyperactivity correlated with the amount of brain 5‐HT accumulating in 1 h after tryptophan loading but not with the overall concentration of brain 5‐HT, suggesting that hyperactivity was dependent upon the rate of 5‐HT synthesis. Reserpine and tetra‐benazine pretreatment speeded the onset and rate of development of the hyperactive state without altering the synthesis of brain 5‐HT. It is suggested that when monoamine oxidase is inhibited and the rate of 5‐HT synthesis is increased, granular uptake and storage of 5‐HT and other rate‐limiting mechanisms for 5‐HT inactivation are unable to prevent 5‐HT 'spilling over’to produce hyperactivity.The crucial dependence of 5‐HT synthesis upon brain tryptophan concentration and the ability of intraneuronal metabolism, when monoamine oxidase activity is intact, to cope with increased 5‐HT synthesis and prevent ‘spillover’, raise the possibility that brain 5‐HT synthesis is normally in excess of functional needs, and suggest that intraneuronal metabolism and the intraneuronal organization of 5‐HT pools are of more importance than synthesis in regulating the amount of 5‐HT available for functional activity.