Responses of neurones in the cerebral cortex and caudate nucleus to amantadine, amphetamine and dopamine.

1. Dopamine amantadine and amphetamine have been applied directly by microiontophoresis to single neurones in the caudate nucleus and cerebral cortex of rats anaesthetized with urethane. 2. The predominant response to all three agents was a depression of neuronal firing rate. The responses to dopamine and amantadine could be antagonized by the dopamine receptor blocking agent, chlorpromazine. 3. Amantadine did not cause any potentiation of dopamine responses, suggesting that inhibition of amine uptake was not responsible for its effects. 4. The responses of pyramidal tract cells in the cerebral cortex to dopamine, amphetamine and amantadine were compared in control groups of rats and rats pretreated with reserpine (10 mg/kg i.p.) or alpha-methyl-p-tyrosine methyl ester (200 mg/kg i.p.). The reduction of cortical catecholamine concentrations was confirmed by a direct fluorimetric assay method. 5. Responses to dopamine were unaltered in the amine-depleted animals compared with controls. Responses to amantadine and amphetamine were reduced but not abolished. 6. It is concluded that amantadine acts partly by releasing catecholamines from neuronal stores. The residual responses to amantadine and amphetamine may be the result of a direct postsynaptic receptor stimulation.