Olanzapine augments the effect of selective serotonin reuptake inhibitors by suppressing GABAergic inhibition via antagonism of 5-HT6 receptors in the dorsal raphe nucleus.

Olanzapine augments the effect of selective serotonin reuptake inhibitors by suppressing GABAergic inhibition via antagonism of 5-HT6 receptors in the dorsal raphe nucleus. Neuropharmacology. 2015 Apr 8; Authors: Asaoka N, Nagayasu K, Nishitani N, Yamashiro M, Shirakawa H, Nakagawa T, Kaneko S Abstract 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 extracell...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research