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| Content Provider | Springer Nature Link |
|---|---|
| Author | du Jardin, Kristian Gaarn Liebenberg, Nico Müller, Heidi Kaastrup Elfving, Betina Sanchez, Connie Wegener, Gregers |
| Copyright Year | 2016 |
| Abstract | The mechanisms mediating ketamine’s antidepressant effect have only been partly resolved. Recent preclinical reports implicate serotonin (5-hydroxytryptamine; 5-HT) in the antidepressant-like action of ketamine. Vortioxetine is a multimodal-acting antidepressant that is hypothesized to exert its therapeutic activity through 5-HT reuptake inhibition and modulation of several 5-HT receptors.The objective of this study was to evaluate the therapeutic-like profiles of S-ketamine, vortioxetine, and the serotonin reuptake inhibitor fluoxetine in response to manipulation of 5-HT tone.Flinders Sensitive Line (FSL) rats, a genetic model of depression, were depleted of 5-HT by repeated administration of 4-chloro-DL-phenylalanine methyl ester HCl (pCPA). Using pCPA-pretreated and control FSL rats, we investigated the acute and sustained effects of S-ketamine (15 mg/kg), fluoxetine (10 mg/kg), or vortioxetine (10 mg/kg) on recognition memory and depression-like behavior in the object recognition task (ORT) and forced swim test (FST), respectively.The behavioral phenotype of FSL rats was unaffected by 5-HT depletion. Vortioxetine, but not fluoxetine or S-ketamine, acutely ameliorated the memory deficits of FSL rats in the ORT irrespective of 5-HT tone. No sustained effects were observed in the ORT. In the FST, all three drugs demonstrated acute antidepressant-like activity but only S-ketamine had sustained effects. Unlike vortioxetine, the antidepressant-like responses of fluoxetine and S-ketamine were abolished by 5-HT depletion.These observations suggest that the acute and sustained antidepressant-like effects of S-ketamine depend on endogenous stimulation of 5-HT receptors. In contrast, the acute therapeutic-like effects of vortioxetine on memory and depression-like behavior may be mediated by direct activity at 5-HT receptors. |
| Starting Page | 2813 |
| Ending Page | 2825 |
| Page Count | 13 |
| File Format | |
| ISSN | 00333158 |
| Journal | Psychopharmacology |
| Volume Number | 233 |
| Issue Number | 14 |
| e-ISSN | 14322072 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2016-05-28 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Serotonin Ketamine Fluoxetine Vortioxetine Antidepressants Forced swim test Object recognition Neurosciences Pharmacology/Toxicology Psychiatry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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