Dopamine prevents muscarinic-induced decrease of glutamate release in the auditory cortex

被引:32
作者
Atzori, M
Kanold, PO
Pineda, JC
Flores-Hernandez, J
Paz, RD
机构
[1] Univ Texas, Sch Behav & Brain Sci, Richardson, TX 75080 USA
[2] Johns Hopkins Univ, Blanchette Rockefeller Neurosci Inst, Rockville, MD USA
[3] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
[4] Ctr Invest Reg Hideyo Noguchi, Merida, Venezuela
[5] Benemerita Univ Autonoma Puebla, Inst Fisiol, Puebla, Mexico
[6] Univ Diego, Dept Psiquiatria & Neurociencia, Portales, Chile
[7] Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA
关键词
acetylcholine; patch-clamp; presynaptic; second-messenger; schizophrenia; neocortex;
D O I
10.1016/j.neuroscience.2005.05.005
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 (A(oxo/) A(ctr)=0.53 +/- 17) in the absence but not in the presence of dopamine (A(oxo)/A(ctr)=0.89 +/- 0.12 in 20 mu M 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. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1153 / 1165
页数:13
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