Widerlöv E, Lewander T
Psychopharmacology (Berl). 1978 Dec 15;60(1):41-5. doi: 10.1007/BF00429177.
Rats were treated chronically with alpha-methyl-p-tyrosine methyl-ester HCl (alpha-MT) twice daily for 0--14 days. At 1 h after the (last) alpha-MT injection, d-amphetamine sulphate was given and motor activity was measured in an ANIMEX activity meter for 4 h. Amphetamine-induced excitatory and stereotyped behaviour was scored according to a rating scale in a separate experiment. A single dose of alpha-MT markedly reduced the activity response after amphetamine. After 1--3 days of alpha-MT treatment, tolerance to its amphetamine-antagonistic affect started to develop, reaching a maximal degree after 7--14 days. The pattern of the amphetamine response, monophasic in control rats, became biphasic in the alpha-MT tolerant rats with an early (at 0--1 h) and a late (2--4 h) peak of motor activity. The late peak appeared within 3 days, while the early peak appeared after 7 days of alpha-MT treatment. The results on amphetamine-induced excitatory and stereotyped behaviour in essence agreed with the motor-activity data. It is concluded that tolerance to the amphetamine-antagonistic action of alpha-MT is not complete. Its rate of development varies in a complex pattern, indicating the presence of more than one mechanism of tolerance.
大鼠每天接受两次α-甲基-对-酪氨酸甲酯盐酸盐（α-MT）的长期治疗，持续0至14天。在（最后一次）α-MT注射后1小时，给予硫酸右苯丙胺，并在ANIMEX活动仪中测量4小时的运动活动。在另一项实验中，根据评分量表对苯丙胺诱导的兴奋和刻板行为进行评分。单剂量的α-MT显著降低了苯丙胺后的活动反应。α-MT治疗1至3天后，对其苯丙胺拮抗作用的耐受性开始发展，在7至14天后达到最大程度。在对照大鼠中呈单相的苯丙胺反应模式，在α-MT耐受大鼠中变为双相，有一个早期（0至1小时）和一个晚期（2至4小时）的运动活动峰值。晚期峰值在3天内出现，而早期峰值在α-MT治疗7天后出现。关于苯丙胺诱导的兴奋和刻板行为的结果在本质上与运动活动数据一致。得出的结论是，对α-MT的苯丙胺拮抗作用的耐受性并不完全。其发展速度以复杂的模式变化，表明存在不止一种耐受机制。
