Facilitation of spontaneous glutamate release by antidepressant drugs in rat locus coeruleus.
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.
Ishibashi
Hitoshi
H
Department of Bio-signaling Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. h-ishi@psysiol2.med.kyushu-u.ac.jp
Eto
Kei
K
Kajiwara
Misako
M
Noda
Mami
M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D008125:Locus Coeruleus / Q000166:cytology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D011189:Potassium Chloride; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione