Resveratrol, a phenol in grapes and wine, reduced locomotor and exploratory activity in mice, decreased exploration of new objects in a memory test, lowered MAO-A activity in the striatum, and increased IL-6 levels in the cortex. When combined with a low dose of ketamine (20 mg/kg), these effects were attenuated, and MAO-A activity also decreased in the cortex. No significant changes in oxidative stress markers were observed. Resveratrol alone did not appear to add to ketamine's effects on behavior, but its own effects on movement and exploration warrant further investigation.
In a mouse model of schizophrenia-like symptoms induced by ketamine, the drug pioglitazone (an activator of PPAR-γ receptors) reversed some of the cognitive and behavioral changes. Ketamine reduced exploration in a novel object recognition test and decreased GAD67 immunoreactivity in the hippocampus. Pioglitazone, given for the last 7 days of a 14-day ketamine regimen, restored performance on the recognition test and normalized hippocampal GAD67 levels. The results suggest that pioglitazone may improve cognitive symptoms associated with schizophrenia, possibly through modulation of GABA-related signaling in the hippocampus.