Article date: January 0001
By: F Pilar‐Cuéllar, R Vidal, A Pazos in Volume 165, Issue 4b, pages 1046-1057
BACKGROUND AND PURPOSE
5‐HT2A 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 β‐catenin protein expression in different cellular fractions, as well as 5‐HT1A 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 β‐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‐HT1A 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‐HT2A receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane‐associated β‐catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5‐HT1A receptor desensitization in the dorsal raphe nucleus.
DOI: 10.1111/j.1476-5381.2011.01516.x
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