Subchronic ketamine treatment leads to permanent changes in EEG, cognition and the astrocytic glutamate transporter EAAT2 in mice
Neurobiology of Disease March 22, 2021 Robert E. Featherstone, Yuling Liang, John A. Saunders et al. 75 citations
Mice given repeated doses of ketamine and then tested after six months of abstinence showed lasting disruptions in brain function and cognition. The animals had reduced amplitude of later auditory event-related potential components (N40 and P80) and diminished stimulus-evoked theta oscillations, indicating impaired information processing. They also displayed deficits in reversal learning and spatial memory. Brain analysis revealed increased astrocyte proliferation and decreased expression of the glial glutamate transporter GLT-1, without signs of neuronal degeneration. These findings suggest that subchronic ketamine induces long-term adaptive or plastic brain changes that persist well beyond drug exposure, closely resembling cognitive impairments seen in human ketamine abusers.