Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex : the dampening action of antidepressants
| Autor: | Giambattista Bonanno, Alessandra Mallei, Daniela Tardito, Laura Musazzi, Pietro Baldelli, Maurizio Popoli, Giorgio Racagni, V.S. Barbiero, Fabio Benfenati, Simona Zappettini, Marco Milanese, Tiziana Bonifacino, Maurizio Raiteri, Pasqualina Farisello |
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| Přispěvatelé: | Musazzi, L, Milanese, M, Farisello, P, Zappettini, S, Tardito, D, Barbiero, V, Bonifacino, T, Mallei, A, Baldelli, P, Racagni, G, Raiteri, M, Benfenati, F, Bonanno, G, Popoli, M |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Mental Health/Neuropsychiatric Disorders lcsh:Medicine Glutamic Acid glutamate Pharmacology gamma-Aminobutyric acid Glutamatergic chemistry.chemical_compound GABA Receptors Glucocorticoid superfused synaptosome Corticosterone Desipramine Neurological Disorders/Neuropsychiatric Disorders medicine Animals Psychiatry Prefrontal cortex lcsh:Science Multidisciplinary antidepressant business.industry lcsh:R Glutamate receptor Glutamic acid Antidepressive Agents Frontal Lobe Rats Neurological Disorders/Neuropharmacology chemistry Excitatory postsynaptic potential Mental Health/Psychopharmacology lcsh:Q molecular mechanism business SNARE Proteins Stress Psychological medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 1, p e8566 (2010) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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