S-Ketamine Mediates Its Acute and Sustained Antidepressant-Like Activity through a 5-HT1B Receptor Dependent Mechanism in a Genetic Rat Model of Depression
| العنوان: | S-Ketamine Mediates Its Acute and Sustained Antidepressant-Like Activity through a 5-HT1B Receptor Dependent Mechanism in a Genetic Rat Model of Depression |
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| المؤلفون: | Gregers Wegener, Betina Elfving, Nico Liebenberg, Manuel Cajina, Connie Sanchez, Kristian Gaarn du Jardin, Heidi Kaastrup Müller |
| المساهمون: | 22353003 - Wegener, Gregers |
| المصدر: | Frontiers in Pharmacology du Jardin, K G, Liebenberg, N, Cajina, M, Müller, H K, Elfving, B, Sanchez, C & Wegener, G 2017, ' 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, vol. 8, pp. 978 . https://doi.org/10.3389/fphar.2017.00978 Frontiers in Pharmacology, Vol 8 (2018) |
| بيانات النشر: | Frontiers Media S.A., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Agonist, ketamine, medicine.drug_class, 5-HT1B receptors, Stimulation, Pharmacology, CP94253, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Genetic model, medicine, Journal Article, Pharmacology (medical), Serotonin (5-hydroxytryptamine, 5-HT), Receptor, Neurotransmitter, 5-HT receptor, forced swim test, Original Research, lcsh:RM1-950, Antidepressants, serotonin (5-hydroxytryptamine, 030227 psychiatry, lcsh:Therapeutics. Pharmacology, 5-HT), chemistry, antidepressants, Ketamine, Forced swim test, Serotonin, 030217 neurology & neurosurgery, Behavioural despair test |
| الوصف: | 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 postsynaptic 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 hr 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. Conclusions:5-HT1B receptor activation during testing appears to be critical for S-ketamine’s antidepressant-like potentials in this model. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1663-9812 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c01b9eb79e0892f34c1603dd2b0624b http://europepmc.org/articles/PMC5775507 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7c01b9eb79e0892f34c1603dd2b0624b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16639812 |
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