Magyar R L, Gillin J C, Wyatt R J
Psychopharmacology (Berl). 1978 Apr 11;56(3):343-50. doi: 10.1007/BF00432859.
The development of tolerance to hyperactivity produced by L-5-hydroxytryptophan (5-HTP) was studied in mice pretreated with the peripheral decarboxylase inhibitor MK-486. The results of Experiment I indicated that partial tolerance developed to 5-HTP given twice daily (i.p.) at a dose of 400 mg/kg, but not at a dose of 800 mg/kg. Sustained hyperactivity at the greater dose (800 mg/kg) apparently resulted from the induction of seizures and stereotypy rather than increased locomotor activity. When 5-HTP (400 mg/kg) or saline was administered three times daily (Experiments II and III), the locomotor activity of saline control groups did not differ significantly from chronic 5-HTP-treated groups, but both differed significantly from that of acute 5-HTP-treated animals. Cessation of treatments resulted in a recovery of 5-HTP-induced hyperactivity for experimental animals when later retested. These findings suggest that mice develop tolerance to the effects of 5-HTP on locomotor activity and agree with the hypothesis that behavior change is more closely correlated with the rate of change in concentration of neurotransmitters than the absolute concentrations.
在经外周脱羧酶抑制剂MK - 486预处理的小鼠中，研究了对L - 5 - 羟色氨酸（5 - HTP）所致多动的耐受性发展情况。实验I的结果表明，对于每天腹腔注射两次、剂量为400mg/kg的5 - HTP产生了部分耐受性，但对于800mg/kg的剂量则未产生耐受性。较高剂量（800mg/kg）下持续的多动显然是由癫痫发作和刻板行为的诱导所致，而非运动活性增加。当每天给予5 - HTP（400mg/kg）或生理盐水三次时（实验II和III），生理盐水对照组的运动活性与慢性5 - HTP处理组无显著差异，但两者均与急性5 - HTP处理动物的运动活性有显著差异。停止处理后，实验动物在随后重新测试时，5 - HTP诱导的多动恢复。这些发现表明小鼠对5 - HTP对运动活性的影响产生了耐受性，并且与行为变化与神经递质浓度变化速率而非绝对浓度更密切相关的假设一致。
