کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5813685 | 1556619 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Olanzapine augments the effect of selective serotonin reuptake inhibitors by suppressing GABAergic inhibition via antagonism of 5-HT6 receptors in the dorsal raphe nucleus
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کلمات کلیدی
5-HTPBSDRNtph2KRHRT-PCRGADMDDDMSO - DMSOMajor depressive disorder - اختلال افسردگی عمدهγ-aminobutyric acid - اسید γ-آمینوبوتیریکDepression - افسردگیOlanzapine - الانزاپینanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceDimethyl sulfoxide - دیمتیل سولفواکسیدSerotonin - سروتونینPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریSelective serotonin reuptake inhibitor - مهار کننده بازجذب سروتونین انتخابیSSRI - مهارکنندههای بازجذب سروتونینGABAergic neurons - نورونهای GABAergicSerotonergic neurons - نورونهای سروتونرژیکdorsal raphe nucleus - هسته رافهtryptophan hydroxylase 2 - هیدروکسیلاز تریپتوفان 2reverse transcription polymerase chain reaction - واکنش زنجیره ای پلیمراز رونویسی معکوسGABA - گاباGlutamate decarboxylase - گلوتامات دکربوکسیلاز5-HT6 receptor - گیرنده 5-HT6
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The combination of the selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotic drugs shows better therapeutic efficacy than SSRI monotherapy in the treatment of depression. However, the underlying mechanisms responsible for the augmenting effects of olanzapine are not fully understood. Here, we report that olanzapine enhances the SSRI-induced increase in extracellular serotonin (5-HT) levels and antidepressant-like effects by inhibiting GABAergic neurons through 5-HT6 receptor antagonism in the dorsal raphe nucleus (DRN). In organotypic raphe slice cultures, treatment with olanzapine (1-100 μM) enhanced the increase in extracellular 5-HT levels in the presence of fluoxetine (10 μM) or citalopram (1 μM). The enhancing effect of olanzapine was not further augmented by the GABAA receptor antagonist bicuculline. Electrophysiological analysis revealed that olanzapine (50 μM) decreased the firing frequency of GABAergic neurons in acute DRN slices. Among many serotonergic agents, the 5-HT6 receptor antagonist SB399885 (1-100 μM) mimicked the effects of olanzapine by enhancing the SSRI-induced increase in extracellular 5-HT levels, which was not further augmented by bicuculline or olanzapine. SB399885 (50 μM) also decreased the firing frequency of GABAergic neurons in the DRN. In addition, an intraperitoneal administration of SB399885 (10 mg/kg) to mice significantly enhanced the antidepressant-like effect of a subeffective dose of citalopram (3 mg/kg) in the tail-suspension test. These results suggest that olanzapine decreases local inhibitory GABAergic tone in the DRN through antagonism of 5-HT6 receptors, thereby increasing the activity of at least part of serotonergic neurons, which may contribute to the augmentation of the efficacy of SSRIs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 95, August 2015, Pages 261-268
Journal: Neuropharmacology - Volume 95, August 2015, Pages 261-268
نویسندگان
Nozomi Asaoka, Kazuki Nagayasu, Naoya Nishitani, Mayumi Yamashiro, Hisashi Shirakawa, Takayuki Nakagawa, Shuji Kaneko,