Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia.
Hippocampus January 1, 2001 R Greene
NMDA antagonists, such as ketamine and phencyclidine, produce psychosis-like effects that model schizophrenia. Circuit analysis in rats shows these drugs selectively disinhibit cortical projection cells in the hippocampus by partially blocking NMDA receptors on interneurons, disrupting the recurrent inhibitory circuit. At low concentrations, this blockade impairs learning and memory, potentially generating abnormal associations. The endogenous peptide NAAG antagonizes NMDA receptors similarly. Enhancing NMDA receptor function is discussed as a possible therapeutic approach for psychosis.