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dc.contributor.authorDu Jardin, Kristian G.
dc.contributor.authorWegener, Gregers
dc.contributor.authorLiebenberg, Nico
dc.contributor.authorCajina, Manuel
dc.contributor.authorMüller, Heidi K.
dc.date.accessioned2018-02-26T08:08:58Z
dc.date.available2018-02-26T08:08:58Z
dc.date.issued2018
dc.identifier.citationDu Jardin, K.G. et al. 2018. S-ketamine mediates its acute and sustained antidepressant-like activity through a 5-HT1B receptor dependent mechanism in a genetic rat model of depression. Frontiers in pharmacology, 8: # 978. [https://doi.org/10.3389/fphar.2017.00978]en_US
dc.identifier.issn1663-9812 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/26433
dc.identifier.urihttps://www.frontiersin.org/articles/10.3389/fphar.2017.00978/full
dc.identifier.urihttps://doi.org/10.3389/fphar.2017.00978
dc.description.abstractRationale: The mechanisms responsible for the unique antidepressant properties of ketamine have only been partly resolved. Recent preclinical reports implicate the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] in the antidepressant-like response of ketamine, and modulation of 5-HT1B receptors has been hypothesized to attain an important role. Objectives: To evaluate the role of endogenous stimulation of 5-HT1B heteroreceptors in the antidepressant-like activity of S-ketamine. Method: Flinders sensitive line (FSL) rats, a genetic model of depression, were depleted of endogenous 5-HT by 4-chloro-DL-phenylalanine methyl ester HCl administration (pCPA; 86 mg/kg/day for 3 days). In pCPA-pretreated and control FSL rats, the acute and sustained effects of a single dose of S-ketamine (15 mg/kg) and the selective 5-HT1B receptor agonist CP94253 (1–6 mg/kg) alone and in combination with S-ketamine were studied in the forced swim test (FST), a commonly used assay that detects antidepressant activity. Results: pCPA pretreatment decreased cortical 5-HT levels to ∼6% but did not affect the baseline behavioral phenotype of FSL rats. S-ketamine demonstrated acute and sustained antidepressant-like activity, both of which were abolished by 5-HT depletion. Combining S-ketamine with a sub-effective dose of CP94253 (1 mg/kg) rescued S-ketamine’s acute and sustained antidepressant-like effects, when CP94253 was administered 2 h prior to the FST. Co-administration of S-ketamine and CP94253 did not affect the plasma level of either compound, suggesting that the observed behavioral interaction could not be ascribed to a kinetic drug-drug interaction. Conclusion: 5-HT1B receptor activation during testing appears to be critical for S-ketamine’s antidepressant-like potentials in this modelen_US
dc.language.isoenen_US
dc.publisherFrontiers Mediaen_US
dc.subjectSerotonin (5-hydroxytryptamine, 5-HT)en_US
dc.subjectKetamineen_US
dc.subjectAntidepressantsen_US
dc.subjectForced swim testen_US
dc.subjectCP94253en_US
dc.subject5-HT1B receptorsen_US
dc.titleS-ketamine mediates its acute and sustained antidepressant-like activity through a 5-HT1B receptor dependent mechanism in a genetic rat model of depressionen_US
dc.typeArticleen_US
dc.contributor.researchID22353003 - Wegener, Gregers


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