dc.contributor.author | Du Jardin, Kristian G. | |
dc.contributor.author | Wegener, Gregers | |
dc.contributor.author | Liebenberg, Nico | |
dc.contributor.author | Cajina, Manuel | |
dc.contributor.author | Müller, Heidi K. | |
dc.date.accessioned | 2018-02-26T08:08:58Z | |
dc.date.available | 2018-02-26T08:08:58Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Du 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.issn | 1663-9812 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/26433 | |
dc.identifier.uri | https://www.frontiersin.org/articles/10.3389/fphar.2017.00978/full | |
dc.identifier.uri | https://doi.org/10.3389/fphar.2017.00978 | |
dc.description.abstract | Rationale: 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 model | en_US |
dc.language.iso | en | en_US |
dc.publisher | Frontiers Media | en_US |
dc.subject | Serotonin (5-hydroxytryptamine, 5-HT) | en_US |
dc.subject | Ketamine | en_US |
dc.subject | Antidepressants | en_US |
dc.subject | Forced swim test | en_US |
dc.subject | CP94253 | en_US |
dc.subject | 5-HT1B receptors | en_US |
dc.title | S-ketamine mediates its acute and sustained antidepressant-like activity through a 5-HT1B receptor dependent mechanism in a genetic rat model of depression | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 22353003 - Wegener, Gregers | |