Brief ReportCellular Mechanisms Underlying the Antidepressant Effects of Ketamine: Role of α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid Receptors
Section snippets
Animals and Treatments
Mice (male, 20–25 g, Jackson Labs, Bar Harbor, Maine) were housed in a standard National Institutes of Health (NIH) animal facility and subjected to experiments after a 1-week accommodation period. Ketamine (.5, 2.5, 10 mg/kg, Sigma, St. Louis, Missouri), MK-801 (also known as Dizocilpine; .05, .1, .2 mg/kg, Sigma), Ro25-6981 (1, 3, 10 mg/kg, Sigma), imipramine (20 mg/kg, Sigma), and 2,3-dihydroxy-6-nitro-7-sulfoamoylbenzo(f)-quinozaline (NBQX; 10 mg/kg, Toronto Research Chemicals, Ontario,
Acute Ketamine Effective in a Model That Requires Repeated Administration of Monoaminergic Antidepressant Drugs
The acute antidepressant-like effect of ketamine was tested with the learned helplessness (LH) paradigm. Mice undergoing the LH paradigm are generally only responsive to monoaminergic antidepressant drugs after repeated administration over several days (16). Significant differences were observed among naïve (without prior helplessness induction), saline-treated, and ketamine-treated groups on escape failures (Figure 1A) and on latency to escape (Figure 1B). In the mice that developed
Discussion
In conclusion, the findings presented here suggest that both nonselective NMDA antagonists as well as NR2B selective antagonists exert their antidepressant effects by regulating the functional interplay between AMPA and NMDA throughput. The results also raise the possibility that the combination of AMPA potentiating agents with even lower doses of NMDA antagonists might have utility in the treatment of depression and is worthy of further study.
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