Loss of the sustained antidepressant-like effect of (2R,6R)-hydroxynorketamine in NMDA receptor GluN2D subunit knockout mice.
Journal of pharmacological sciences March 1, 2024 Aimi Yamagishi, Yuiko Ikekubo, Masayoshi Mishina et al. 6 citations
The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) produces both immediate and lasting antidepressant-like effects in mice, while its stereoisomer (2S,6S)-HNK does not. The sustained effects depend on the GluN2D subunit of the NMDA receptor: they disappear in mice lacking this subunit, although the acute effects remain. In stressed wildtype mice, GluN2B protein expression decreases in the nucleus accumbens, but this decrease does not occur in GluN2D-knockout mice. These findings suggest that the GluN2D subunit, and possibly GluN2B, mediate the long-lasting antidepressant-like action of (2R,6R)-HNK.