AMPHETAMINE ATTENUATES THE STIMULATED RELEASE OF DOPAMINE INVIVO

Abstract

C-fiber voltammetric electrodes were used to measure the release of dopamine in the caudate nucleus of an anesthetized rat. Release was induced by electrical stimulation of the medial forebrain bundle. The amplitude of the observed release was attentuated by i.p. injection of amphetamine. A similar attenuation was induced by reserpine at a slower rate. The combined regimen of amphetamine (1 or 10 mg/kg) and electrical stimulation did not deplete striatal dopamine levels and thus the decreased release of dopamine was not a result of depleted dopamine stores. Benztropine (25 mg kg-1) was 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) did not affect the stimulated release. Haloperidol (1.0 mg kg-1) increased the amount of DA release, but was unable to attenuate the inhibition caused by amphetamine. The actions induced by amphetamine are apparently 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 mechanism for the observed in vivo actions of amphetamine.