The interactive effects of Ketamine and Magnesium on Brain-Derived Neurotrophic Factor (BDNF) and depressive-like behavior (P4.080)
Sara Razmjou, Darcy Litteljohn, Shawn P. Hayley
Neurology April 6, 2015 DOI: 10.1212/wnl.84.14_supplement.p4.080 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled animal experiment Peer reviewed |
|---|---|
| Sample size | 96 |
| Population | CD1 mice |
| Interventions | Ketamine Magnesium |
| Dose | Acute: ketamine 2.5 mg/kg, 5 mg/kg, and 10 mg/kg; chronic: ketamine 15 mg/kg |
| Duration | Acute experiment: single intervention; chronic experiment: two weeks of magnesium injections followed by a single ketamine injection, with assessments 24 hours after the last magnesium injection |
| Measures | Western immunoblotting for BDNF, forced swim test immobility time |
| Topics | Esketamine Ketamine |
| Key findings | Acute co-administration of magnesium and ketamine increased prefrontal cortex BDNF expression only at 2.5 mg/kg ketamine, without behavioral effects, while higher ketamine doses and chronic magnesium treatment showed no significant benefit on BDNF levels or immobility time. The authors suggest acute magnesium-ketamine may have a synergistic effect on prefrontal BDNF but conclude further research is needed. |
Abstract
Objective: To evaluate the potential synergistic effect of ketmaine and magnesium treatment on prefrontal cortex (PFC) and hippocampal BDNF expression and depressive-like behavior in mice model.
Background: Ketamine, an NMDA receptor antagonist with neuroplastic effect on up-regulation of BDNF, has been investigated significantly as a fast acting antidepressant particularly in treatment resistant depression. However, due to its abuse potential and serious side effects at higher doses, co-administration with synergistic drugs including magnesium (Mg) is under study. Design/Methods: The effects of acute and chronic Mg treatment, co-administered with a single dose of Ketamine were assessed on mice model of depression/ acute stress induced by forced swim test. BDNF levels in PFC and hippocampus were assessed using western immunoblotting. Depressive-like behavior defined as immobility time in forced swim test was evaluated 1 hour after intervention. In an acute setting, 64 CD1 mice were randomly divided into 8 groups in a two (Mg vs saline) by four (saline vs ketamine 2.5mg/kg, 5mg/kg and 10mg/kg) ANOVA design. In another chronic setting, 32 CD1 mice received two weeks intra-peritoneal injections of magnesium. 24 hours after the last injection, they received saline or ketmaine (15mg/kg) and then they were assessed for BDNF expression and depressive-like behavior.
Results: In the acute experiment, Mg-ketamine combination therapy increased PFC BDNF expression only at the dose of 2.5mg/kg ketamine ( F(3,56)= 3.11, P=0.035) without any behavioral consequences (F(3,64)= 0.564, P=0.641). In the chronic Mg experiment with a single ketamine injection, no significant effect was observed on PFC BDNF levels (F(1,32)=1.244, p=0.356), hippocampal BDNF levels (F(1,32)=0.08, p=0.90), or immobility time in FST (F(1,30)= 5.2, P=0.031).
Conclusion: While chronic mg administration shows no benefit, acute co-administration of mg and ketamine may have synergistic effect on increasing PFC BDNF expression. Further research is warranted to ascertain potential adjunctive effect of mg and ketamine. Disclosure: Dr. Razmjou has nothing to disclose. Dr. Litteljohn has nothing to disclose. Dr. Hayley has nothing to disclose.
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 |