Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression
Molecular Brain June 16, 2020 L. Aleksandrova, Y. Wang, A. Phillips 87 citations
A single low dose of ketamine or its metabolite (2R,6R)-HNK rescues impaired long-term potentiation in the dorsal hippocampus of Wistar-Kyoto rats, a model of depression, with effects appearing after 3.5 hours and persisting for 24 hours. The same treatments restore long-term spatial memory deficits in these rats. However, only ketamine, not (2R,6R)-HNK, produces rapid and sustained effects in the forced swim test, a screen for antidepressant-like activity. This dissociation indicates that restoring hippocampal synaptic plasticity is not linked to ketamine's effects in the forced swim test but may contribute to reversing cognitive deficits, supporting the theory that ketamine reverses stress-induced loss of neural connectivity by engaging synaptic plasticity.