Dataset Information
Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, ?-catenin and antidepressant-like effects.
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ABSTRACT: Background and purpose
5-HT(2A) receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically.Experimental approach
Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2'-deoxyuridine (BrdU) incorporation, and ?-catenin protein expression in different cellular fractions, as well as 5-HT(1A) receptor function were measured in the hippocampus of rats treated with fluoxetine, ketanserin and fluoxetine + ketanserin for 7 days, followed by a forced swimming test (FST) to analyse antidepressant efficacy.Key results
mRNA for BDNF was increased in the CA3 field and dentate gyrus of the hippocampus by combined treatment with fluoxetine + ketanserin. Expression of ?-catenin was increased in total hippocampal homogenate and in the membrane fraction, but unchanged in the nuclear fraction after combined treatment with fluoxetine + ketanserin. These effects were paralleled by a decreased immobility time in the FST. There were no changes in BrdU incorporation, TrkB expression and 5-HT(1A) receptor function in any of the groups studied.Conclusions and implications
The antidepressant-like effect induced by subchronic co-treatment with a SSRI and a 5-HT(2A) receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane-associated ?-catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5-HT(1A) receptor desensitization in the dorsal raphe nucleus.
SUBMITTER: Pilar-Cuellar F
PROVIDER: S-EPMC3346247 | biostudies-literature | 2012 Feb
REPOSITORIES: biostudies-literature
Publications
Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, β-catenin and antidepressant-like effects.
British journal of pharmacology 20120201 4b
<h4>Background and purpose</h4>5-HT(2A) receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically.<h4>Experimental approach</h4>Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2'-deoxyu ...[more]