Amphetamine attenuates the stimulated release of dopamine in vivo

Carbon-fiber voltammetric electrodes have been used to measure the release of dopamine in the caudate nucleus of an anesthetized rat. Release is induced by electrical stimulation of the medial forebrain bundle. The amplitude of the observed release is attenuated by i.p. injection of amphetamine. A similar attenuation is induced by reserpine; however, at a slower rate. The combined regimen of amphetamine (1 or 10 mg/kg) and electrical stimulation does not deplete striatal dopamine levels and thus the decreased release of dopamine is not a result of depleted dopamine stores. Benztropine (25 mg kg^-1) is able to cause a short term inhibition of the action of amphetamine (1 mg kg^-1). The dopamine agonist pergolide (0.5 mg kg^-1) does not affect the stimulated release. Haloperidol (1.0 mg kg^-1) increases the amount of DA release, but is unable to attenuate the inhibition caused by amphetamine. Thus, it appears that the actions induced by amphetamine are a result of interaction with the neuronal uptake carrier and subsequent transport of dopamine from a functional to nonfunctional pool. In isolated striatal synaptic vesicles, amphetamine is found to block dopamine uptake and induce its release. This in vitro evidence provides a possible mechamism for the observed in vivo actions of amphetamine.