Effects of psychotomimetic and antipsychotic agents on neocortical and striatal concentrations of various amino acids in the rat
Effects of psychotomimetic and antipsychotic agents on neocortical and striatal concentrations of various amino acids in the rat
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DOI：
10.1111/j.1471-4159.2004.02592.x
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发表时间：
2004-09-01
影响因子：
4.7
通讯作者：
Nishikawa, T
中科院分区：
文献类型：
--
作者：
Sakurai, S;Ishii, S;Nishikawa, T
皮下注射小剂量和中等剂量（1.6，3.2，4.0和4.8 mg/kg）的拟精神分裂症的甲基苯丙胺引起的L-Arg和L-Asn的组织含量（净含量）在新皮层和纹状体在60分钟，但不是在360分钟，注射后剂量相关的增加。甲基苯丙胺（4.8 mg/kg）诱导的这些氨基酸水平的增加显着衰减预处理抗精神病药物，氟哌啶醇（1 mg/kg）或氯氮平（10 mg/kg）。在新皮层，氯氮平可逆的增加水平的L-Thr也观察到甲基苯丙胺给药后60分钟。纹状体浓度的L-Glu，L-Ser，L-Thr，Gly和L-Ala增加了相同的方案在氟哌啶醇和氯氮平敏感的方式。中等剂量的另一种拟精神分裂症苯环利定（7.5毫克/公斤）皮下给药诱导强大的异常行为，减少在新皮层和纹状体水平的L-Asp和纹状体的L-Ala含量的增加，而没有显着影响的其他氨基酸的研究。这些结果表明，新皮层和纹状体L-Arg，L-Asn，L-Thr，Gly，L-Ala或L-Ser可能参与甲基苯丙胺的拟精神病作用，并可能与大脑多巴胺能传递相互作用。甲基苯丙胺和苯环利定对各种氨基酸的净新皮层和纹状体浓度的不同影响可能，至少部分地，是这两种药物引起的精神病的不同特征的基础。
A subcutaneous injection of small and moderate doses (1.6, 3.2, 4.0 and 4.8 mg/kg) of the schizophrenomimetic methamphetamine caused a dose-related increase in the tissue content (the net content) of L-Arg and L-Asn in the neocortex and striatum at 60 min, but not at 360 min, after injection. The methamphetamine-induced (4.8 mg/kg) increases in levels of these amino acids were significantly attenuated by pretreatment with an antipsychotic drug, haloperidol (1 mg/kg) or clozapine (10 mg/kg). In the neocortex, a clozapine-reversible increase in the level of L-Thr was also observed 60 min after methamphetamine administration. Striatal concentrations of L-Glu, L-Ser, L-Thr, Gly and L-Ala were augmented by the same regimen in a haloperidol- and clozapine-sensitive fashion. A moderate dose of another schizophrenomimetic phencyclidine (7.5 mg/kg) given subcutaneously induced robust abnormal behavior, a diminution in the neocortical and striatal levels of L-Asp and an increase in the striatal L-Ala content without significant effects on the other amino acids studied. These results suggest that neocortical and striatal L-Arg, L-Asn, L-Thr, Gly, L-Ala or L-Ser may be implicated in the psychotomimetic effects of methamphetamine and might display mutual interaction with cerebral dopaminergic transmission. The differential effects of methamphetamine and phencyclidine on the net neocortical and striatal concentrations of various amino acids might, at least in part, underlie the distinct features of psychoses induced by these two drugs.