Abstract

Amphetamine inhibited the neuronal uptake and accumulation of ³H-norepinephrine into chopped rat brain tissue. The concentration required for half-maximal effect (EC50) was 0.71 µM. When amphetamine was added to tissue which had previously accumulated ³H-norepinephrine, there was a concentration-related (EC50, 2.5 µM) efflux of ³H-norepinephrine from the tissue to the incubation medium. Cocaine and desipramine were approximately equipotent with amphetamine in inhibiting neuronal uptake but differed in their ability to release the ³H-amine. The EC5O for release of ³H-norepinephrine by cocaine was approximately the same as amphetamine but the maximal release produced by cocaine was much less than that of amphetamine. Desipramine, on the other hand, inhibited neuronal uptake maximally at concentrations which caused little or no release of ³H-norepinephrine. Since amphetamine, cocaine and desipramine have approximately the same potency in inhibiting neuronal uptake but differ in their ability to release, it is concluded that amphetamine-induced release of ³H-norepinephrine is not simply due to inhibition of neuronal uptake of spontaneously released ³H-amine. When the release of ³H-norepinephrine by d-amphetamine and potassium chloride was studied in the presence of concentrations of cocaine or desipramine which markedly inhibit neuronal uptake, the concentration-effect curve for amphetamine was shifted to the right. The same concentration of cocaine had no effect on the release of ³H-norepinephrine by potassium chloride. The uptake of low concentrations of ³H-amphetamine into synaptosomes from cerebral cortex was markedly inhibited by cocaine and desipramine. These results indicate that amphetamine is transported by the neuronal uptake system and that cocaine and desipramine inhibit the release of ³H-norepinephrine at low concentrations of amphetamine by inhibiting the transport of amphetamine into the neuron.