INVOLVEMENT OF NIGRO-STRIATAL NEURONS IN THE IN VIVO RELEASE OF DOPAMINE BY AMPHET-AMINE, AMANTADINE AND TYRAMINE

Abstract

After labeling the caudate nucleus of spinal-sectioned cats with 3H-dopamine and perfusing the cerebroventricular system, d - or l -amphetamine, amantadine or tyramine was added to the perfusion inflow. All four drugs caused a concentration-related efflux of 3H-dopamine into the ventricular effluent. When the experiment was repeated using cats with chronic lesions of the nigro-striatal dopaminergic fibers, the drug-evoked efflux was greatly reduced. When similar lesions were made during perfusate collection. a significant drop in 3H-dopamine efflux occurred. The ability of amphetamine and amantadine to increase 3H-dopamine efflux was markedly decreased by this acute lesion; the efflux indueed by tyramine was unaffected. Low concentrations of amphetamine or amantadine but not tyramine, potentiated the efflux of 3H-dopamine elicited by low frequency nigro-striatal pathway stimulation. Thus, the efflux of 3H-dopamine evoked from central dopaminergic synapses by amphetamine and amantadine is primarily dependent upon the impulse activity of neurons in the nigro-striatal pathway; the release by tyramine, although arising from the same terminals, is not dependent upon ongoing impulse activity.