Mireia Tarrés-Gatius

2 papers in the library · publishing 2020-2022

Papers

Discrimination of motor and sensorimotor effects of phencyclidine and MK-801: Involvement of GluN2C-containing NMDA receptors in psychosis-like models.

Neuropharmacology August 1, 2022 Mireia Tarrés-Gatius, Ximena López-Hill, Lluis Miquel-Rio et al.

Non-competitive NMDA receptor antagonists like PCP and MK-801 produce schizophrenia-like effects, but the specific receptor subunits and brain regions involved are unclear. Using GluN2C knockout mice, the authors found that deleting the GluN2C subunit reduced stereotyped behaviors such as circling, rearing, and ataxia signs induced by PCP and MK-801, indicating better motor coordination. However, other motor effects and sensorimotor gating deficits (pre-pulse inhibition) remained unchanged. PCP and MK-801 activated c-fos in thalamo-cortical networks but reduced it in the cerebellum, with differences between genotypes matching motor coordination changes. Resting-state fMRI showed enhanced cortico-thalamic-cerebellar connectivity in knockout mice that was less disrupted by MK-801. Thus, GluN2C-containing NMDA receptors in cerebellar circuits mediate some motor incoordination effects but not sensorimotor gating deficits.

DOI: 10.1016/j.neuropharm.2022.109079 Full text Brain activity Cerebellum Non-competitive nmda-r antagonists Schizophrenia +1

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.

DOI: 10.1038/s41398-020-01110-y Full text Biology Medicine Psychology