Effects of acute and chronic amphetamine treatment on Purkinje neuron discharge in rat cerebellum.

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.