Document Detail

Facilitation of spontaneous glutamate release by antidepressant drugs in rat locus coeruleus.
MedLine Citation:
PMID:  15644283     Owner:  NLM     Status:  MEDLINE    
The effects of antidepressant drugs on spontaneous excitatory postsynaptic currents (EPSCs) were investigated in the mechanically dissociated rat locus coeruleus (LC) neurons which had their presynaptic nerve terminals attached. The membrane currents were recorded by the whole-cell patch-clamp technique. Desipramine, a tricyclic antidepressant, reversibly and concentration-dependently increased the frequency of spontaneous EPSCs, but did not alter their amplitude distribution. The inhibitors of high-voltage-activated Ca2+ channels failed to block the facilitatory action of desipramine, while they inhibited the high K+-induced facilitation of spontaneous EPSC frequency. The desipramine action was also observed in the absence of extracellular Ca2+. Pretreatment of thapsigargin in Ca2+-free solution fully inhibited the desipramine action, thus suggesting the involvement of Ca2+ release from intracellular Ca2+ stores at glutamatergic presynaptic nerve terminals. Imipramine and nortriptyline, other tricyclic antidepressants, and amoxapine, mianserin and fluoxetine, non-tricyclic antidepressants, also increased the EPSC frequency, while tranylcypromine, an inhibitor of monoamine oxidase, did not increase the glutamate release. The present results indicate that modulation of spontaneous glutamatergic transmission by tricyclic- and non-tricyclic-antidepressant drugs may regulate the excitability of LC neurons.
Hitoshi Ishibashi; Kei Eto; Misako Kajiwara; Mami Noda
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience letters     Volume:  374     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-12     Completed Date:  2005-03-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  152-6     Citation Subset:  IM    
Department of Bio-signaling Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
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MeSH Terms
6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
Action Potentials / drug effects,  physiology
Animals, Newborn
Antidepressive Agents / pharmacology*
Calcium Channel Blockers / pharmacology
Cells, Cultured
Dose-Response Relationship, Drug
Drug Interactions
Excitatory Amino Acid Antagonists / pharmacology
Excitatory Postsynaptic Potentials / drug effects
Glutamic Acid / metabolism*
Locus Coeruleus / cytology*
Neurons / drug effects*,  physiology
Patch-Clamp Techniques / methods
Potassium Chloride / pharmacology
Rats, Wistar
Reg. No./Substance:
0/Antidepressive Agents; 0/Calcium Channel Blockers; 0/Excitatory Amino Acid Antagonists; 115066-14-3/6-Cyano-7-nitroquinoxaline-2,3-dione; 56-86-0/Glutamic Acid; 7447-40-7/Potassium Chloride

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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