Dopaminergic terminal excitability following arrival of the nerve impulse: The influence of amphetamine and haloperidol

Abstract

Variations in the excitability of the axons and terminal fields of dopaminergic neurons of the substantia nigra were examined as a function of time following the nerve impulse in urethane-anesthetized, immobilized rats. Excitability was measured by determining the threshold, defined as the minimum current required to consistently activate dopaminergic neurons antidromically. Threshold currents were maximal immediately following the action potential and declined exponentially to a plateau. The interval during which threshold currents declined, the phasic period, was significantly longer for stimulation of neostriatal terminal fields as contrasted to stimulation of axons along the medial forebrain bundle. A positive correlation was observed between antidromic response latency and the duration of this phasic period for both sites of stimulation, an observation consistent with the view that the site of initiation of the antidromic action potential is of smaller diameter in the neostriatum than in the medial forebrain bundle Amphetamine, which promotes dopamine release and/or re-uptake blockade, reduced dopaminergic terminal excitability in the neostriatum at all intervals examined. This effect increased at successively shorter intervals during the phasic portion of the excitability curve. Haloperidol, a dopamine antagonist, increased the excitability of dopaminergic terminal fields, an effect which was also more marked earlier in the phasic interval. Neither amphetamine nor haloperidol had a significant effect on the excitability of dopaminergic axons in the medial forebrain bundle. Variations in dopaminergic terminal excitability after impulse arrival, and the effects of amphetamine and haloperidol on this phenomenon suggest that terminal excitability is determined by events related to arrival of the nerve impulse including activation of presynaptic ‘autoreceptors’ by dopamine released from the synaptic ending.