Freedman R, Marwaha J
J Pharmacol Exp Ther. 1980 Mar;212(3):390-6.
The spontaneous discharge of the cerebellar Purkinje neuron in urethane-anesthetized rats is used as an indicator of central noradrenergic activity during the acute and chronic administration of d-amphetamine. Acute parenteral administration of amphetamine causes a dose-dependent slowing of the discharge. Since this effect is not seen in animals in which the catecholaminergic innervation has been selectively removed by previous treatment with 6-hydroxydopamine, it is hypothesized that the slowing is caused by the increased release and/or blocked reuptake of endogenous norepinephrine. Acute administration of amphetamine also increases the response of the Purkinje neurons to its afferent inputs: the excitatory climbing fibers and the inhibitory basket and stellate cells. These effects of amphetamine on spontaneous and evoked activity are similar to the effects of microiontophoretically applied norepinephrine. After daily treatment for 5 days with amphetamine, there is no change in the response to acutely administered amphetamine. After 21 days of treatment, discharge rates before and after acute administration are both significantly lower than in acutely treated controls. Administration of the beta adrenergic antagonist propranolol returns the discharge rate to control levels in these chronically treated animals. Chronic amphetamine treatment may thus cause an increase in response to endogenous norepinephrine, both when spontaneously released and when released after acute amphetamine administration.
在乌拉坦麻醉的大鼠中，小脑浦肯野神经元的自发放电被用作在急性和慢性给予右旋苯丙胺期间中枢去甲肾上腺素能活性的指标。急性肠胃外给予苯丙胺会导致放电呈剂量依赖性减慢。由于在用6-羟基多巴胺预先处理选择性去除了儿茶酚胺能神经支配的动物中未观察到这种效应，因此推测这种减慢是由内源性去甲肾上腺素释放增加和/或再摄取受阻引起的。急性给予苯丙胺还会增加浦肯野神经元对其传入输入的反应：兴奋性攀缘纤维以及抑制性篮状细胞和星状细胞。苯丙胺对自发和诱发活动的这些作用类似于微量离子电泳施加去甲肾上腺素的作用。在用苯丙胺每日治疗5天后，对急性给予苯丙胺的反应没有变化。治疗21天后，急性给药前后的放电率均显著低于急性治疗的对照组。在这些长期治疗的动物中，给予β肾上腺素能拮抗剂普萘洛尔可使放电率恢复到对照水平。因此，慢性苯丙胺治疗可能会导致对内源性去甲肾上腺素的反应增加，无论是在自发释放时还是在急性给予苯丙胺后释放时。
