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.
Wednesday, April 22 2015, 7:30 am-12:00 pm
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