論文

査読有り
2013年11月

Chronic effects of antidepressants on serotonin release in rat raphe slice cultures: high potency of milnacipran in the augmentation of serotonin release

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
  • Kazuki Nagayasu
  • ,
  • Maiko Kitaichi
  • ,
  • Naoya Nishitani
  • ,
  • Nozomi Asaoka
  • ,
  • Hisashi Shirakawa
  • ,
  • Takayuki Nakagawa
  • ,
  • Shuji Kaneko

16
10
開始ページ
2295
終了ページ
2306
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1017/S1461145713000771
出版者・発行元
CAMBRIDGE UNIV PRESS

Most clinically-used antidepressants acutely increase monoamine levels in synaptic clefts, while their therapeutic effects often require several weeks of administration. Slow neuroadaptive changes in serotonergic neurons are considered to underlie this delayed onset of beneficial actions. Recently, we reported that sustained exposure of rat organotypic raphe slice cultures containing abundant serotonergic neurons to selective serotonin (5-HT) reuptake inhibitors (citalopram, fluoxetine and paroxetine) caused the augmentation of exocytotic serotonin release. However, the ability of other classes of antidepressants to evoke a similar outcome has not been clarified. In this study, we investigated the sustained actions of two tricyclic antidepressants (imipramine and desipramine), one tetracyclic antidepressant (mianserin), three 5-HT and noradrenaline reuptake inhibitors (milnacipran, duloxetine and venlafaxine) and one noradrenergic and specific serotonergic antidepressant (mirtazapine) on serotonin release in the slice cultures. For seven of nine antidepressants, sustained exposure to the agents at concentrations of 0.1-100 mu m augmented the level of increase in extracellular serotonin. The rank order of their potency was as follows: milnacipran>duloxetine>citalopram>venlafaxine>imipramine>fluoxetine>desipramine. Neither mirtazapine nor mianserin caused any augmentation. The highest augmentation by sustained exposure to milnacipran was partially attenuated by an alpha(1)-adrenoceptor antagonist, benoxathian, while the duloxetine-, venlafaxine- and citalopram-mediated increases were not affected. These results suggest that inhibition of the 5-HT transporter is required for the enhancement of serotonin release. Furthermore, the potent augmentation by milnacipran is apparently due to the accompanied activation of the alpha(1)-adrenoceptor.

リンク情報
DOI
https://doi.org/10.1017/S1461145713000771
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23920436
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000326558300014&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-84885605195&partnerID=MN8TOARS
URL
http://orcid.org/0000-0001-5152-5809
ID情報
  • DOI : 10.1017/S1461145713000771
  • ISSN : 1461-1457
  • eISSN : 1469-5111
  • ORCIDのPut Code : 25904671
  • PubMed ID : 23920436
  • SCOPUS ID : 84885605195
  • Web of Science ID : WOS:000326558300014

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