Dopamine inhibition of evoked IPSCs in rat prefrontal cortex.
Rat prefrontal cortex (PFC) receives substantial dopamine (DA) input. This DA innervation appears critical for modulation of PFC cognitive functions. Clinical and experimental studies have also implicated DA in the pathogenesis of a number of neurological and psychiatric disorders including epilepsy and schizophrenia. However, the actions of DA at the cellular level are incompletely understood. Both inhibitory interneurons and pyramidal cells are targets of DA and may express different DA receptor types. Our recent findings suggest that DA can directly excite cortical interneurons and increase the frequency of spontaneous inhibitory postsynaptic currents (IPSCs). The present study was undertaken to determine the effect of specific DA receptor agonists on evoked (e) IPSCs. Visually identified pyramidal neurons were studied using whole cell voltage-clamp techniques. Bath application of DA 30 microM reduced IPSC amplitude to 80 +/- 4% (mean +/- SE) of control without any significant change in IPSC kinetics or passive membrane properties. The D1-like DA receptor agonist SKF 38393 reduced IPSC amplitude to 71.5 +/- 8%, whereas the D2-like specific agonist quinpirole has no effect on amplitude (94.5 +/- 5%). The D1-like receptor antagonist SCH 23390 prevented DA inhibition of IPSC amplitude (98.2 +/- 4%), whereas IPSCs were still reduced in amplitude (79.7 +/- 4%) by DA in the presence of the D2-like receptor antagonist sulpiride. DA increased significantly paired-pulse inhibition, whereas responses to puff applied GABA were unaffected. Addition of the PKA inhibitor H-8 blocked the effect of DA on IPSCs. These results suggest that DA can decrease IPSCs in layer II-III PFC neocortical pyramidal cells by activating presynaptic D1-like receptors.
Gonzalez-Islas
C
C
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Hablitz
J J
JJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003864:Depression, Chemical; D004298:Dopamine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D017447:Receptors, Dopamine D1; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine