Abstract

Glutamatergic dysfunction may play an important role in both the pathophysiology of schizophrenia, and impaired memory commonly observed in that disorder. NMDA receptor antagonists impair learning/memory in animal models, putatively based on its ability to block long-term potentiation (LTP) in the hippocampus. Although well studied in animal models, research in humans is limited and confounded by administration of NMDA antagonists before the learning experience. Based on presumed glutamatergic dysfunction, it was predicted that the NMDA antagonist ketamine would not effect memory in schizophrenic subjects. Bolus injections of ketamine (0.5 mg/kg) or placebo were given to seven patients with schizophrenia in this double-blind cross-over study. Immediately prior to injection, subjects were administered verbal and figural memory tests. Delayed recalls were obtained 30–45 min postinjection. In order to rule out drug-induced generalized cognitive impairments, other cognitive tasks were administered pre- and postinjection. The results indicate no differences between the drug and placebo conditions for either memory task, and no changes on the other cognitive tasks observed.

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