title: D2 receptor regulation of synaptic burst firing in prefrontal cortical pyramidal neurons.
abstract: The efficacy of antipsychotics in the treatment of schizophrenia depends on their ability to block dopamine (DA) D2 receptors. D2 receptor excitatory mediation of glutamatergic receptors has been implicated in in vivo studies. However, D2 receptor enhancement of glutamatergic transmission has rarely been reported in slice recordings. Instead, D2 receptor depression of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) action was obtained in previous slice studies. To obtain insight into this paradox, we examined DA's actions on synaptic responses of layer V pyramidal cells to minimal extracellular stimulation in layer III of ferret prefrontal cortical slices under NMDA and gamma-aminobutyric acid type A blockade. This experimental design models the proposed hypofunction of NMDA receptor and gamma-aminobutyric acid type A deficiency in schizophrenia. We found that DA and D2 receptor agonists promoted burst firing in a subset of pyramidal cells, which was reversed by haloperidol, a D2 antagonist and a D3 agonist, compounds having antipsychotic efficacy. In contrast, a D4 antagonist, which has not proven clinically effective, was not effective in blocking DA-promoted bursts. These results revealed excitatory effects of DA mediated mainly via D2 receptors, potentially providing a cellular mechanism for the D2 antagonism in treating schizophrenia.
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA. yun-wang@yale.edu
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Goldman-Rakic
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D005289:Ferrets; D009474:Neurons / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: D017447:Receptors, Dopamine D1