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The P-glycoprotein inhibitor cyclosporin A differentially influences behavioural and neurochemical responses to the antidepressant escitalopram

Overview of attention for article published in Behavioural Brain Research, November 2013
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Title
The P-glycoprotein inhibitor cyclosporin A differentially influences behavioural and neurochemical responses to the antidepressant escitalopram
Published in
Behavioural Brain Research, November 2013
DOI 10.1016/j.bbr.2013.11.027
Pubmed ID
Authors

Fionn E. O’Brien, Richard M. O’Connor, Gerard Clarke, Maria D. Donovan, Timothy G. Dinan, Brendan T. Griffin, John F. Cryan

Abstract

Recent studies have raised the possibility that P-glycoprotein (P-gp) inhibition may represent a putative augmentation strategy for treatment with certain antidepressants. Indeed, we have previously shown that administration of the P-gp inhibitor verapamil increased the brain distribution and behavioural effects of the antidepressant escitalopram. The aim of the current study was to investigate if similar effects occur with another P-gp inhibitor, cyclosporin A (CsA). CsA pre-treatment exacerbated the severity of behaviours in an escitalopram-induced mouse model of serotonin syndrome, a potentially life-threatening adverse drug reaction associated with serotonergic drugs. P-gp inhibition by CsA enhanced the brain distribution of escitalopram by 70-80%. Serotonin (5-HT) turnover in the prefrontal cortex was reduced by escitalopram, and this effect was augmented by CsA. However, CsA pre-treatment did not augment the effect of escitalopram in the tail suspension test (TST) of antidepressant-like activity. Microdialysis experiments revealed that pre-treatment with CsA failed to augment, but blunted, the increase in extracellular 5-HT in response to escitalopram administration. This blunting effect may contribute to the lack of augmentation in the TST. Taken together, the present studies demonstrate that co-administration of CsA and escitalopram produces differential effects depending on the behavioural and neurochemical assays employed. Thus, the results highlight the need for further studies involving more selective pharmacological tools to specifically evaluate the impact of P-gp inhibition on behavioural responses to antidepressants which are subject to efflux by P-gp.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Ireland 1 3%
Canada 1 3%
Unknown 27 93%

Demographic breakdown

Readers by professional status Count As %
Professor > Associate Professor 6 21%
Student > Ph. D. Student 5 17%
Student > Master 5 17%
Student > Bachelor 4 14%
Researcher 2 7%
Other 5 17%
Unknown 2 7%
Readers by discipline Count As %
Medicine and Dentistry 6 21%
Agricultural and Biological Sciences 6 21%
Pharmacology, Toxicology and Pharmaceutical Science 3 10%
Biochemistry, Genetics and Molecular Biology 2 7%
Neuroscience 2 7%
Other 4 14%
Unknown 6 21%
Attention Score in Context

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 07 October 2014.
All research outputs
#17,286,379
of 25,374,647 outputs
Outputs from Behavioural Brain Research
#3,167
of 4,975 outputs
Outputs of similar age
#201,064
of 315,186 outputs
Outputs of similar age from Behavioural Brain Research
#33
of 64 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,975 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 315,186 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 64 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.