Browne R G, Segal D S
Pharmacol Biochem Behav. 1977 May;6(5):545-52. doi: 10.1016/0091-3057(77)90115-0.
Previous studies have shown that repeated administration of d-amphetamine results in a progressive augmentation of locomotor activity and stereotypy. The present studies demonstrate that rats also exhibit an enhanced behavioral response following multiple daily injections of l-amphetamine and methylphenidate. Furthermore, behavioral augmentation is shown to persist for at least six days after a single injection of d-amphetamine. These results demonstrate the generality of the reverse tolerance phenomenon and indicate that metabolic factors, such as the formation of false neurotransmitters, do not account for the enhanced behavioral responsiveness observed with multiple injections of these drugs. The role of experiential factors in the behavioral augmentation was studied by (1) varying the amount of continuous exposure to the experimental environment prior to d-amphetamine administration, and (2) examining the effects of repeated injections of saline or d-amphetamine in different environments prior to testing in the experimental chambers. The results, which revealed a behavioral augmentation independent of pretreatment condition, indicate that neither acclimation to the test chamber nor state-dependent conditioning to external stimuli accounts for the enhanced locomotor activity and stereotypy observed with repeated administration of psychomotor stimulants.
以往的研究表明，重复给予右旋苯丙胺会导致运动活动和刻板行为逐渐增强。目前的研究表明，大鼠在每日多次注射左旋苯丙胺和哌甲酯后也表现出增强的行为反应。此外，单次注射右旋苯丙胺后，行为增强至少持续六天。这些结果证明了反向耐受现象的普遍性，并表明代谢因素，如假神经递质的形成，不能解释多次注射这些药物后观察到的行为反应增强。通过以下方式研究了经验因素在行为增强中的作用：（1）在给予右旋苯丙胺之前，改变对实验环境的持续暴露量；（2）在实验箱中进行测试之前，检查在不同环境中重复注射生理盐水或右旋苯丙胺的效果。结果显示行为增强与预处理条件无关，这表明适应测试箱或对外部刺激的状态依赖性条件作用都不能解释重复给予精神运动兴奋剂后观察到的运动活动增强和刻板行为。
