Effects of haloperidol on the activity and membrane physiology of substantia nigra dopamine neurons recorded in vitro

A variety of experimental evidence suggests that one function of dendritically released dopamine is the feedback modulation of dopamine neuron firing rate via stimulation of the somatodendritic autoreceptors located on these cells. Under these conditions, blockade of these receptors should result in an alteration in the firing rate of dopamine neurons. In order to test this prediction, we have examined whether haloperidol alters the electrophysiological activity of dopamine neurons recorded from nigral slices maintained in vitro. This preparation permits examination of the effects of haloperidol when the substantia nigra is isolated from long-loop afferent cell populations, and also facilitates the performance of intracellular recordings to allow the assessment of alterations in membrane properties that underlie any changes in firing rate. Addition of haloperidol to the media bathing nigral slices caused increases in the spontaneous firing rate of some dopamine neurons. It also caused depolarization of the membrane and increases in input resistance in a subset of dopamine neurons. However, this drug had no consistent effects on the delayed repolarization or the anomalous rectification that are characteristic of activity in these cells. Morphological assessment of dopamine neurons stained in the coronal sections used in these studies confirmed that the dendrites of dopamine neurons were largely intact in these slices. These results demonstrate that blockade of the somatodendritic autoreceptors located on dopamine neurons does cause alterations in the electrophysiological activity of these cells, substantiating the role of nigral dopamine release in the modulation of dopamine neuron activity.