Dopamine decreases the excitability of layer V pyramidal cells in the rat prefrontal cortex

  • Gulledge A
  • Jaffe D
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Abstract

In both primates and rodents, the prefrontal cortex (PFC) is highly innervated by dopaminergic fibers originating from the ventral tegmental area, and activation of this mesocortical dopaminergic system decreases spontaneous and evoked activity in the PFC in vivo. We have examined the effects of dopamine (DA), over a range of concentrations, on the passive and active membrane properties of layer V pyramidal cells from the rat medial PFC (mPFC). Whole-cell and perforated-patch recordings were made from neurons in rat mPFC. As a measure of cell excitability, trains of action potentials were evoked with 1-sec-long depolarizing current steps. Bath application of DA (0.05-30 microM) produced a reversible decrease in the number of action potentials evoked by a given current step. In addition, DA reversibly decreased the input resistance (RN) of these cells. In a subset of experiments, a transient increase in excitability was observed after the washout of DA. Control experiments suggest that these results are not attributable to changes in spontaneous synaptic activity, age-dependent processes, or strain-specific differences in dopaminergic innervation and physiology. Pharmacological analyses, using D1 agonists (SKF 38393 and SKF 81297), a D1 antagonist (SCH 23390), a D2 receptor agonist (quinpirole), and a D2 antagonist (sulpiride) suggest that decreases in spiking and RN are mediated by D2 receptor activation. Together, these results demonstrate that DA, over a range of concentrations, has an inhibitory effect on layer V pyramidal neurons in the rat mPFC, possibly through D2 receptor activation

Author-supplied keywords

  • Action Potentials
  • Age Factors
  • Animals
  • Animals,Newborn
  • D2
  • Dopamine Agonists
  • Dopamine Antagonists
  • Electrophysiology
  • In Vitro
  • Neurons
  • Patch-Clamp Techniques
  • Prefrontal Cortex
  • Primates
  • Pyramidal Cells
  • Quinpirole
  • Rats
  • Rats,Long-Evans
  • Rats,Sprague-Dawley
  • Receptors,Dopamine D1
  • Receptors,Dopamine D2
  • SCH 23390
  • Sch-23390
  • Sulpiride
  • Support,U.S.Gov't,P.H.S.
  • Temperature
  • Ventral Tegmental Area
  • agonist
  • agonists
  • antagonists & inhibitors
  • dopamine
  • drug effects
  • innervation
  • pharmacology
  • physiology
  • primate
  • rat

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  • PMID: 9787016

Authors

  • A T Gulledge

  • D B Jaffe

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