(R)-ketamine attenuates neurodevelopmental disease-related phenotypes in a mouse model of maternal immune activation

Eur Arch Psychiatry Clin Neurosci. 2023 May 30. doi: 10.1007/s00406-023-01629-3. Online ahead of print.ABSTRACTInfections during pregnancy are associated with an increased risk of neuropsychiatric disorders with developmental etiologies, such as schizophrenia and autism spectrum disorders (ASD). Studies have shown that the animal model of maternal immune activation (MIA) reproduces a wide range of phenotypes relevant to the study of neurodevelopmental disorders. Emerging evidence shows that (R)-ketamine attenuates behavioral, cellular, and molecular changes observed in animal models of neuropsychiatric disorders. Here, we investigate whether (R)-ketamine administration during adolescence attenuates some of the phenotypes related to neurodevelopmental disorders in an animal model of MIA. For MIA, pregnant Swiss mice received intraperitoneally (i.p.) lipopolysaccharide (LPS; 100 µg/kg/day) or saline on gestational days 15 and 16. The two MIA-based groups of male offspring received (R)-ketamine (20 mg/kg/day; i.p.) or saline from postnatal day (PND) 36 to 50. At PND 62, the animals were examined for anxiety-like behavior and locomotor activity in the open-field test (OFT), as well as in the social interaction test (SIT). At PND 63, the prefrontal cortex (PFC) was collected for analysis of oxidative balance and gene expression of the cytokines IL-1β, IL-6, and TGF-β1. We show that (R)-ketamine abolishes anxiety-related behavior and social interaction deficits induced by MIA. A...
Source: European Archives of Psychiatry and Clinical Neuroscience - Category: Psychiatry Authors: Source Type: research