Chronic effects of antidepressants on serotonin release in rat raphe slice cultures: high potency of milnacipran in the augmentation of serotonin release
- PMID:23920436
- DOI: 10.1017/S1461145713000771
Chronic effects of antidepressants on serotonin release in rat raphe slice cultures: high potency of milnacipran in the augmentation of serotonin release
Abstract
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 μ 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 α 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 α 1-adrenoceptor.
Similar articles
- Utility of organotypic raphe slice cultures to investigate the effects of sustained exposure to selective 5-HT reuptake inhibitors on 5-HT release.Nagayasu K, Yatani Y, Kitaichi M, Kitagawa Y, Shirakawa H, Nakagawa T, Kaneko S.Nagayasu K, et al.Br J Pharmacol. 2010 Dec;161(7):1527-41. doi: 10.1111/j.1476-5381.2010.00978.x.Br J Pharmacol. 2010.PMID:20698856Free PMC article.
- Acute effect of milnacipran on the relationship between the locus coeruleus noradrenergic and dorsal raphe serotonergic neuronal transmitters.Bandoh T, Hayashi M, Ino K, Takada S, Ushizawa D, Hoshi K.Bandoh T, et al.Eur Neuropsychopharmacol. 2004 Dec;14(6):471-8. doi: 10.1016/j.euroneuro.2004.01.003.Eur Neuropsychopharmacol. 2004.PMID:15589386
- Designing a new generation of antidepressant drugs.Pinder RM.Pinder RM.Acta Psychiatr Scand Suppl. 1997;391:7-13. doi: 10.1111/j.1600-0447.1997.tb05953.x.Acta Psychiatr Scand Suppl. 1997.PMID:9265946
- Preclinical pharmacology of milnacipran.Briley M, Prost JF, Moret C.Briley M, et al.Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:9-14. doi: 10.1097/00004850-199609004-00002.Int Clin Psychopharmacol. 1996.PMID:8923122Review.
- Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications.Caccia S.Caccia S.Clin Pharmacokinet. 1998 Apr;34(4):281-302. doi: 10.2165/00003088-199834040-00002.Clin Pharmacokinet. 1998.PMID:9571301Review.
Cited by
- Gut microbe-derived milnacipran enhances tolerance to gut ischemia/reperfusion injury.Deng F, Hu JJ, Lin ZB, Sun QS, Min Y, Zhao BC, Huang ZB, Zhang WJ, Huang WK, Liu WF, Li C, Liu KX.Deng F, et al.Cell Rep Med. 2023 Mar 21;4(3):100979. doi: 10.1016/j.xcrm.2023.100979.Cell Rep Med. 2023.PMID:36948152Free PMC article.
- Potassium 2-(1-hydroxypentyl)-benzoate improves depressive-like behaviors in rat model.Ma H, Wang W, Xu S, Wang L, Wang X.Ma H, et al.Acta Pharm Sin B. 2018 Oct;8(6):881-888. doi: 10.1016/j.apsb.2018.08.004. Epub 2018 Aug 20.Acta Pharm Sin B. 2018.PMID:30505657Free PMC article.
- Endogenous 5-HT outflow from chicken aorta by 5-HT uptake inhibitors and amphetamine derivatives.Delgermurun D, Ito S, Ohta T, Yamaguchi S, Otsuguro K.Delgermurun D, et al.J Vet Med Sci. 2016 Jan;78(1):71-6. doi: 10.1292/jvms.15-0146. Epub 2015 Aug 29.J Vet Med Sci. 2016.PMID:26321443Free PMC article.
- Comparison of Protective Effects of Antidepressants Mediated by Serotonin Receptor in Aβ-Oligomer-Induced Neurotoxicity.Yamamoto K, Tsuji M, Oguchi T, Momma Y, Ohashi H, Ito N, Nohara T, Nakanishi T, Ishida A, Hosonuma M, Nishikawa T, Murakami H, Kiuchi Y.Yamamoto K, et al.Biomedicines. 2024 May 23;12(6):1158. doi: 10.3390/biomedicines12061158.Biomedicines. 2024.PMID:38927365Free PMC article.
- Generation of functional human serotonergic neurons from fibroblasts.Vadodaria KC, Mertens J, Paquola A, Bardy C, Li X, Jappelli R, Fung L, Marchetto MC, Hamm M, Gorris M, Koch P, Gage FH.Vadodaria KC, et al.Mol Psychiatry. 2016 Jan;21(1):49-61. doi: 10.1038/mp.2015.161. Epub 2015 Oct 27.Mol Psychiatry. 2016.PMID:26503761
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials