Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9425352 | Neuroscience | 2005 | 13 Pages |
Abstract
Acetylcholine and dopamine are simultaneously released in the cortex at the occurrence of novel stimuli. In addition to a series of excitatory effects, acetylcholine decreases the release of glutamate acting on presynaptic muscarinic receptors. By recording evoked excitatory postsynaptic currents in layers II/III neurons of the auditory cortex, we found that activation of muscarinic receptors by oxotremorine reduces the amplitude of glutamatergic current (Aoxo/Actr=0.53±0.17) in the absence but not in the presence of dopamine (Aoxo/Actr=0.89±0.12 in 20μM dopamine). These data suggested that an excessive sensitivity to dopamine, such as postulated in schizophrenia, could prevent the decrease of glutamate release associated with the activation of cholinergic corticopetal nuclei. Thus, a possible mechanism of action of antipsychotic drugs could be through a depression of the glutamatergic signal in the auditory cortex. We tested the capability of haloperidol, clozapine and lamotrigine to affect glutamatergic synaptic currents and their muscarinic modulation. We found that antipsychotics not only work as dopamine receptor antagonists in re-establishing muscarinic modulation, but also directly depress glutamatergic currents. These results suggest that presynaptic modulation of glutamate release can account for a dual route of action of antipsychotic drugs.
Keywords
presynapticmEPSCsPPRD-2-amino-5-phosphonopentanoic acideEPSCNMDARPKCevoked excitatory postsynaptic current4-DAMPPLCAPVTTXaCSFHEPESpKaAMPAcyclic AMPcAMPDMSOEPSCN-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid)AChAcetylcholineSchizophreniaα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acidDAROxooxotremorinetetrodotoxinexcitatory postsynaptic currentDopaminedimethylsulphoxidepertussis toxinphospholipase Cartificial cerebrospinal fluidpaired pulse rationeocortexprotein kinase AProtein kinase CPatch-clampMuscarinic receptorN-methyl-d-aspartate receptorDopamine receptor
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Authors
M. Atzori, P.O. Kanold, J.C. Pineda, J. Flores-Hernandez, R.D. Paz,