Integrative role for serotonergic and glutamatergic receptor mechanisms in the action of NMDA antagonists: potential relationships to antipsychotic drug actions on NMDA antagonist responsiveness.
George R. Breese, Darin J Knapp, Sheryl S Moy
Neuroscience and biobehavioral reviews June 2002 DOI: 10.1016/s0149-7634(02)00011-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Key findings | The authors argue that NMDA receptor antagonists produce schizophrenia-like behavioral and neurochemical effects in animals and humans, and that these effects are reduced by 5-HT(2A) antagonists, mGLU2 agonists, and atypical antipsychotics more than typical ones. They propose that clarifying how antipsychotics differ in chronic efficacy against NMDA antagonist neuropathology could reveal mechanisms underlying the core pathogenesis of schizophrenia. |
Abstract
NMDA receptor antagonists worsen symptoms in schizophrenia and induce schizophrenic-like symptoms in normal individuals. In animals, NMDA antagonist-induced behavioral responses include increased activity, head weaving, deficits in paired pulse inhibition and social interaction, and increased forced swim immobility. Repeated exposure to NMDA antagonists in animals results in behavioral sensitization-a phenomenon accentuated in rats with dopaminergic neurons lesioned during development. In keeping with an involvement of serotonin and glutamate release in NMDA antagonist action, selected behaviors induced by NMDA antagonists are minimized by 5-HT(2A) receptor antagonists and mGLU2 receptor agonists. These observations provide promising new approaches for treating acute NMDA antagonist-induced psychosis. Further, acute atypical antipsychotic drugs also minimize NMDA antagonist actions to a greater degree than typical antipsychotics. However, because knowledge concerning acute versus chronic effectiveness of various antipsychotic drugs against NMDA antagonist neuropathology is limited, future studies to define more fully the basis of their differences in efficacy after chronic treatment could provide an understanding of their actions on neural mechanisms responsible for the core pathogenesis of schizophrenia.
Comparable studies
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