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Ketamine’s Effect on Brain Could Help Explain Mechanisms Behind Psychosis
An investigation into how the NMDA receptor inhibitor ketamine affects the brains of rats may lead to a better understanding of the causes of psychosis in people with schizophrenia. Researchers reported the results of their study in the European Journal of Neuroscience.
“The discovered alterations in thalamic and cortical electrical activity associated with ketamine-induced sensory information processing disorders could serve as biomarkers for testing antipsychotic drugs or predicting the course of disease in patients with psychotic spectrum disorders,” said Sofya Kulikova, PhD, a senior research fellow at the National Research University Higher School of Economics, in Perm, Russia.
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In healthy individuals, the noncompetitive NMDA receptor antagonist ketamine can induce a mental state similar to psychosis, the research team explained. This includes disturbances in sensory-related broadband beta-/gamma-frequency (17-29 Hz/30-80 Hz) oscillations in corticothalamic networks.
“In normal healthy subjects and rodents, complex integration processes, like sensory perception, induce transient, large-scale synchronized beta/gamma oscillations in a time window of a few hundred ms (200-700 ms) after the presentation of the object of attention (eg, sensory stimulation),” researchers wrote. “Our goal was to use an electrophysiological multisite network approach to investigate, in lightly anesthetized rats, the effects of a single psychotomimetic dose (2.5 mg/kg, subcutaneous) of ketamine on sensory stimulus-induced oscillations.”
Researchers monitored rat responses to having their whiskers stimulated before and after ketamine administration. Microelectrodes implanted in the animals recorded electrical activity in the thalamus and the somatosensory cortex, a region of the brain responsible for processing sensory information from the thalamus.
Ketamine increased the power of beta and gamma oscillations in the cortex and the thalamus, even in the resting state before the stimulus occurred, the research team reported. The amplitude of beta/gamma oscillations in the 200–700 ms post-stimulus period at each cortical and thalamic site was significantly lower following ketamine administration, which appears to be associated with impaired perception.
By inhibiting NMDA receptors, ketamine also added noise to gamma frequencies in the post-stimulation period in one thalamic nucleus and in one layer of the somatosensory cortex, analysis showed. This noise increase further impaired the ability of neurons to process incoming sensory signals, researchers believe.
“The present findings support the hypothesis that NMDA receptor antagonism disrupts the transfer of perceptual information in the somatosensory cortico-thalamo-cortical system,” researchers wrote.
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