Ketamine and fluoxetine exert similar actions on prelimbic and infralimbic responsivity to lateral septal nucleus stimulation in Wistar rats.
Carlos M Contreras, Ana G Gutiérrez-García
Neuroscience Letters June 21, 2024 DOI: 10.1016/j.neulet.2024.137848 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Wistar rats |
| Interventions | Ketamine Fluoxetine |
| Dose | anesthetic dose of ketamine, high dose of fluoxetine |
| Duration | 24 h after drug administration |
| Topics | Ketamine Esketamine |
| Keywords | Fluoxetine Infralimbic cortex Lateral septal nucleus Prelimbic cortex Neuropharmacology psychopharmacology Depression treatment antidepressants Mood disorders Psychiatric medication Neural networks Brain connectivity |
| Citations | 4 |
| Key points | Ketamine and fluoxetine both accentuate inhibition of the lateral septal nucleus action on the medial prefrontal cortex, suggesting a common forebrain pathway for antidepressant effects. |
Abstract
Ketamine is a dissociative anesthetic that has been proposed to be a useful alternative in cases of a poor response to other treatments in patients with depression. Remarkably, beneficial clinical actions of ketamine are detected once its psychotropic actions disappear. Therefore, clinical actions may occur independently of dose. Most current studies focus on actions of ketamine on neurotrophic factors, but few studies have investigated actions of ketamine on neural structures for which actions of antidepressants have been previously explored. Lateral septal nucleus (LSN) stimulation reduces neural activity in the prelimbic cortex (PL) and infralimbic cortex (IL) subregions of the medial prefrontal cortex (mPFC). Fluoxetine increases inhibitory responsivity of the LSN-IL connection. In the present study, actions of an anesthetic dose of ketamine were compared with a high dose of fluoxetine on behavior and neural responsivity 24 h after drug administration. Fluoxetine reduced immobility in the forced swim test without changing locomotor activity in the open field test. Ketamine strongly decreased locomotor activity and did not produce changes in immobility. In another set of Wistar rats that received similar drug treatment regimens, the results indicated that LSN stimulation in saline-treated animals produced a long-lasting inhibitory afterdischarge in these mPFC subregions. Actions of ketamine on the LSN-mPFC connection reproduced actions of fluoxetine, consisting of accentuated inhibition of the LSN action on the mPFC. These findings suggest that independent of different actions on neurotransmission, the common final pathway of antidepressants lies in their actions on forebrain structures that are related to emotional regulation.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 10
- Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression The International Journal of Neuropsychopharmacology October 8, 2013
- Neurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine. Pharmacology, Biochemistry, and Behavior December 9, 2019
- Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency? The Journal of Clinical Psychiatry July 20, 2017
- Ketamine and the Future of Rapid-Acting Antidepressants Annual Review of Clinical Psychology February 9, 2021
- Ketamine and its metabolites: Potential as novel treatments for depression. Neuropharmacology October 1, 2022
and 5 more in the library