| Title |
5-HT2A receptor inactivation potentiates the acute antidepressant-like activity of escitalopram: involvement of the noradrenergic system
|
|---|---|
| Published in |
Experimental Brain Research, February 2013
|
| DOI | 10.1007/s00221-013-3434-3 |
| Pubmed ID | |
| Authors |
G. Quesseveur, C. Repérant, D. J. David, A. M. Gardier, C. Sanchez, B. P. Guiard |
| Abstract |
Evidence suggests that the serotonin 2A receptor (5-HT2AR) modulates the therapeutic activity of selective serotonin reuptake inhibitors (SSRIs). Indeed, among the genetic factors known to influence the individual response to antidepressants, the HTR2A gene has been associated with SSRIs response in depressed patients. However, in these pharmacogenetic studies, the consequences of HTR2A gene polymorphisms on 5-HT2AR expression or function are lacking and the precise role of this receptor is still matter of debate. This study examined the effect of 5-HT2AR agonism or antagonism with DOI and MDL100907, respectively, on the serotonergic system and the antidepressant-like activity of the SSRI escitalopram in mouse. The 5-HT2AR agonist DOI decreased the firing rate of 5-HT neurons in the dorsal raphe (DR) nucleus of 5-HT2AR(+/+) anesthetized mice. This inhibitory response persisted in 5-HT2CR(-/-) but was completely blunted in 5-HT2AR(-/-) mutants. Moreover, the suppressant effect of DOI on DR 5-HT neuronal activity in 5-HT2AR(+/+) mice was attenuated by the loss of noradrenergic neurons induced by the neurotoxin DSP4. Conversely, in 5-HT2AR(+/+) mice, the pharmacological inactivation of the 5-HT2AR by the selective antagonist MDL100907 reversed escitalopram-induced decrease in DR 5-HT neuronal activity. Remarkably, in microdialysis experiments, a single injection of escitalopram increased cortical extracellular 5-HT, but not NE, levels in awake 5-HT2AR(+/+) mice. Although the addition of MDL100907 did not potentiate 5-HT neurotransmission, it allowed escitalopram to increase cortical NE outflow and consequently to elicit an antidepressant-like effect in the forced swimming test. These results suggest that the blockade of the 5-HT2AR may strengthen the antidepressant-like effect of escitalopram by facilitating the enhancement of the brain NE transmission. They provide support for the use of atypical antipsychotics with SSRIs as a relevant antidepressant augmentation strategy. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 2 | 3% |
| United Kingdom | 1 | 2% |
| Unknown | 57 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 14 | 23% |
| Student > Ph. D. Student | 10 | 17% |
| Student > Master | 10 | 17% |
| Other | 4 | 7% |
| Student > Doctoral Student | 3 | 5% |
| Other | 11 | 18% |
| Unknown | 8 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 18 | 30% |
| Agricultural and Biological Sciences | 12 | 20% |
| Medicine and Dentistry | 7 | 12% |
| Biochemistry, Genetics and Molecular Biology | 5 | 8% |
| Psychology | 2 | 3% |
| Other | 4 | 7% |
| Unknown | 12 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 March 2014.
All research outputs
#18,329,207
of 22,696,971 outputs
Outputs from Experimental Brain Research
#2,472
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Outputs of similar age
#238,025
of 307,673 outputs
Outputs of similar age from Experimental Brain Research
#25
of 40 outputs
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