Acute Stress Increases Depolarization-Evoked Glutamate Release in the Rat Prefrontal/Frontal Cortex: The Dampening Action of Antidepressants

被引：232

作者：

Musazzi, Laura ^{[1
,2
]}

Milanese, Marco ^{[3
,6
,7
]}

Farisello, Pasqualina ^{[4
,7
,8
]}

Zappettini, Simona ^{[3
,6
,7
]}

Tardito, Daniela ^{[1
,2
]}

Barbiero, Valentina S. ^{[1
,2
]}

Bonifacino, Tiziana ^{[3
,6
,7
]}

Mallei, Alessandra ^{[1
,2
]}

Baldelli, Pietro ^{[4
,7
,8
]}

Racagni, Giorgio ^{[1
,2
,3
,4
,5
,6
,7
,8
]}

Raiteri, Maurizio ^{[3
,6
,7
]}

Benfenati, Fabio ^{[4
,7
,8
]}

Bonanno, Giambattista ^{[3
,6
,7
]}

Popoli, Maurizio ^{[1
,2
]}

机构：

[1] Univ Milan, Dept Pharmacol Sci, Ctr Neuropharmacol, Milan, Italy

[2] Univ Milan, Ctr Excellence Neurodegenerat Dis, Milan, Italy

[3] Univ Genoa, Dept Expt Med, Sect Pharmacol & Toxicol, Genoa, Italy

[4] Italian Inst Technol, Dept Neurosci & Brain Technol, Genoa, Italy

[5] Ist Ricovero & Cura Carattere Sci San Giovanni di, Brescia, Italy

[6] Ctr Excellence Biomed Res, Genoa, Italy

[7] Natl Inst Neurosci, Genoa, Italy

[8] Univ Genoa, Dept Expt Med, Physiol Sect, Genoa, Italy

来源：

PLOS ONE | 2010年 / 5卷 / 01期

关键词：

MINERALOCORTICOID RECEPTORS; MAJOR DEPRESSION; MEMBRANE-FUSION; FRONTAL-CORTEX; MESSENGER-RNA; SNARE COMPLEX; HIPPOCAMPUS; SYNAPTOSOMES; BRAIN; CORTICOSTERONE;

D O I：

10.1371/journal.pone.0008566

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release. Methodology/Findings: Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine) and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated), and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486). On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats). Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability. Conclusions/Significance: Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress, shown here for the first time, could be related to the therapeutic action of these drugs.

引用

页数：11

共 55 条

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