Modulation by dopamine D1-like receptors of synaptic transmission and NMDA receptors in rat nucleus accumbens is attenuated by the protein kinase C inhibitor Ro 32-0432.
Dopamine, acting at a D1-like receptor, depresses the release of glutamate in the nucleus accumbens (NAcc) in brain slices, thereby reducing the amplitude of the excitatory postsynaptic current (EPSC). This effect depends upon an inhibitory feedback action of adenosine, liberated following facilitation of postsynaptic NMDA receptors by D1 receptor activation, an action independent of adenylyl cyclase stimulation or cyclic AMP-dependent protein kinase (PKA; Harvey, J., Lacey, M.G., 1997. J. Neurosci. 17, 5271). Using whole-cell recording from NAcc neurones, the dopamine depression of the EPSC was blocked by pre-treatment of brain slices with the selective protein kinase C (PKC) inhibitor Ro 32-0432, but only minimally attenuated by intracellular dialysis of single cells with Ro 32-0432 in the recording pipette. With synaptic transmission blocked by tetrodotoxin, inward currents caused by application of NMDA were enhanced by the D1 receptor agonist SKF 81297A in half the cells tested. In a separate population of cells dialysed intracellularly with Ro 32-0432, SKF 81297A was without effect on NMDA current amplitude. These findings indicate a functional role for phospholipase C-coupled D1-like receptors in both modulating synaptic transmission in NAcc and potentiating NMDA receptors on a subset of NAcc neurones, via PKC activation.
Chergui
K
K
Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, UK.
Lacey
M G
MG
D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; C085989:Ro 32-0432; D011493:Protein Kinase C; D004298:Dopamine