Autoreceptor-mediated changes in dopaminergic terminal excitability: effects of increases in impulse flow.

The effect of spontaneous and stimulation-induced alterations in impulse flow on the antidromic excitability of nigrostriatal dopaminergic neurons were investigated in urethane-anesthetized rats. Terminal excitability was found to be inversely related to the rate of spontaneous activity of nigral neurons. Conditioning stimulation applied to dopaminergic axons in the medial forebrain bundle was found to decrease terminal excitability, but axonal conditioning stimulation was without effect on antidromic responses evoked from the medial forebrain bundle. Decreases in terminal excitability induced by medial forebrain bundle stimulation could be blocked by local infusions of haloperidol into the region of the terminal fields, suggesting that the effect was receptor-mediated. These results are consistent with the proposal that nigrostriatal dopaminergic neurons may modulate the impulse-dependent release of dopamine from striatal nerve terminals as a function of firing rate by autoreceptor-mediated alterations in the electrical properties of the terminal membrane.