DOPAMINE DECREASES THE EXCITABILITY OF LAYER-V PYRAMIDAL CELLS IN THERAT PREFRONTAL CORTEX

In both primates and rodents, the prefrontal cortex (PFC) is highly in nervated by dopaminergic fibers originating from the ventral tegmental area, and activation of this mesocortical dopaminergic system decreas es spontaneous and evoked activity in the PFC in vivo. We have examine d the effects of dopamine (DA), over a range of concentrations, on the passive and active membrane properties of layer V pyramidal cells fro m the rat medial PFC (mPFC). Whole-cell and perforated-patch recording s were made from neurons in rat mPFC. As a measure of cell excitabilit y, trains of action potentials were evoked with 1-sec-long depolarizin g current steps. Bath application of DA (0.05-30 mu M) produced a reve rsible decrease in the number of action potentials evoked by a given c urrent step. In addition, DA reversibly decreased the input resistance (R-N) of these cells. In a subset of experiments, a transient increas e in excitability was observed after the washout of DA. Control experi ments suggest that these results are not attributable to changes in sp ontaneous synaptic activity, age-dependent processes, or strain-specif ic differences in dopaminergic innervation and physiology. Pharmacolog ical analyses, using D1 agonists (SKF 38393 and SKF 81297), a D1 antag onist (SCH 23390), a 02 receptor agonist (quinpirole), and a D2 antago nist (sulpiride) suggest that decreases in spiking and R-N are mediate d by D2 receptor activation. Together these results demonstrate that D A, over a range of concentrations, has an inhibitory effect on layer V pyramidal neurons in the rat mPFC, possibly through D2 receptor activ ation.