Involvement of NMDA receptors containing the GluN2C subunit in the psychotomimetic and antidepressant-like effects of ketamine
Translational Psychiatry December 1, 2020 Mireia Tarrés-Gatius, L. Miquel-Rio, L. Campa et al.
Ketamine produces rapid antidepressant effects but also perceptual disturbances similar to those caused by PCP. The brain networks involved are not fully understood, but both drugs activate thalamo-cortical networks by blocking NMDA receptors in the reticular thalamic nucleus. This study examined whether the GluN2C subunit of the NMDA receptor, densely expressed in the thalamus and cerebellum, mediates these effects using wild-type and GluN2C knockout mice of both sexes. GluN2C deletion dramatically reduced ketamine-induced circling behavior in both sexes, but the antidepressant-like effect was fully preserved. Some sex differences in c-fos expression and glutamate levels were observed. The GluN2C subunit may distinguish between ketamine's antidepressant and psychotomimetic actions, and cerebellar NMDA receptors may contribute to some behavioral effects.