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发育期间的膳食锂:大鼠脑中氨基酸水平、离子含量及[3H]螺哌隆结合的变化

Dietary lithium during development: changes in amino acid levels, ionic content, and [3H]spiperone binding in the brain of rats.

作者信息

Wajda I J, Banay-Schwartz M, De Guzman T, Manigault I

出版信息

Neurochem Res. 1983 May;8(5):637-48. doi: 10.1007/BF00964703.

DOI:10.1007/BF00964703
PMID:6412150
Abstract

We found that chronic lithium diet affects the sensitivity of neuroleptic receptors and the content of amino acids in the brain, and that the changes in adult animals differ from those in young rats. Pregnant rats were kept on lithium diet (pellets with 0.21% Li2CO3 and 0.21% NaCl) during the gestation period and the offspring were kept on lithium for six weeks after delivery. Control rats were kept on normal diet under identical conditions. In corpus striatum and cerebral cortex of lithium-treated young rats a reduction in apparent dissociation constant and no change in (3H)spiperone total binding sites were found, suggesting a sensitization of the neuroleptic receptor; this result was unlike that obtained with adult lithium-treated rats, where the total number of binding sites was decreased. The lithium content of brain was very high (2.32 meq/kg of wet weight), whereas in the serum only 0.75 meq/l was recorded. K+ and Na+ levels increased by 20% and 9% respectively in the brain and remained at normal levels in the serum. Analysis of free amino acids in the cerebral cortex, midbrain, and cerebellum showed increases in GABA and glycine levels in all three regions, a significant increase in taurine in midbrain, and an increase in lysine in cerebral cortex and cerebellum. The results indicate that the effect of chronic dietary lithium given during pregnancy on the neuroleptic receptor in young rats is different from that in adult animals. It produces an increase in the number of the neuroleptic receptor sites instead of the decline in the number of binding sites found in adult rats. It remains to be established whether this effect is related more to the age of the animal tested or to the stage of development of the CNS at which the lithium was administered.

摘要

我们发现,长期锂饮食会影响脑内抗精神病药物受体的敏感性以及氨基酸含量,且成年动物的变化与幼鼠不同。妊娠大鼠在妊娠期食用锂饮食(含0.21%Li₂CO₃和0.21%NaCl的颗粒饲料),其后代在产后继续食用锂饮食六周。对照大鼠在相同条件下食用正常饮食。在接受锂处理的幼鼠的纹状体和大脑皮层中,发现表观解离常数降低,(³H)司哌罗宁总结合位点无变化,提示抗精神病药物受体致敏;这一结果与成年锂处理大鼠不同,成年大鼠的结合位点总数减少。脑内锂含量非常高(湿重2.32 meq/kg),而血清中仅记录到0.75 meq/l。脑内K⁺和Na⁺水平分别升高20%和9%,血清中则维持在正常水平。对大脑皮层、中脑和小脑游离氨基酸的分析表明,所有三个区域的GABA和甘氨酸水平均升高,中脑牛磺酸显著升高,大脑皮层和小脑赖氨酸升高。结果表明,孕期给予的长期饮食锂对幼鼠抗精神病药物受体的影响与成年动物不同。它使抗精神病药物受体位点数量增加,而非成年大鼠中发现的结合位点数量减少。这种效应是更多地与受试动物的年龄相关,还是与给予锂时中枢神经系统的发育阶段相关,仍有待确定。

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引用本文的文献

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Modulation of the serotonin S2-receptor in brain after chronic lithium.慢性锂治疗后大脑中5-羟色胺S2受体的调节
Neurochem Res. 1986 Jul;11(7):949-57. doi: 10.1007/BF00965585.
2
Effects of sodium, lithium, and magnesium on in vitro binding of [3H]SCH23390 in rat neostriatum and cerebral cortex.
Neurochem Res. 1989 May;14(5):419-26. doi: 10.1007/BF00964855.

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