Prefrontal NMDA receptor antagonism reduces impairments in pre-attentive information processing.
Daniel Klamer, Lennart Svensson, Kim Fejgin, Erik Pålsson
European Neuropsychopharmacology March 2011 DOI: 10.1016/j.euroneuro.2010.10.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Phencyclidine (PCP) |
| Dose | Prefrontal PCP 0.01, 0.1, or 1 mM; systemic PCP 5 mg/kg |
| Measures | Prepulse inhibition (PPI) |
| Key points | Prefrontal cortex injection of phencyclidine at 0.1 mM ameliorated prepulse inhibition deficits induced by systemic phencyclidine (5 mg/kg), whereas prefrontal phencyclidine alone at 0.01, 0.1, or 1 mM did not affect prepulse inhibition. The authors conclude that prefrontal NMDA receptor blockade alone is insufficient to impair prepulse inhibition but may be a key factor in the prepulse inhibition-disruptive effects of global NMDA receptor inhibition. |
Abstract
A well established theory proposes that glutamate signalling via the NMDA receptor is compromised in patients with schizophrenia. Deficits related to NMDA receptor signalling can be observed in several brain regions including the prefrontal cortex (PFC), an area extensively linked to the cognitive dysfunction in this disease and notably affected by NMDA receptor antagonists such as phencyclidine (PCP). In addition, a number of studies suggest that normalizing of PFC function could constitute a treatment rationale for schizophrenia. To further study the role of PFC function we investigated the effect of local PFC NMDA receptor blockade on impaired prepulse inhibition (PPI) induced by systemic administration of PCP. Mice received prefrontal injections of PCP (0.01, 0.1 or 1mM) before PCP treatment (5mg/kg) and were thereafter tested for PPI. PCP induced deficits in PPI were ameliorated by prefrontal PCP (0.1mM) treatment whereas PPI was not affected by prefrontal cortex PCP administration per se at any of the doses tested. Taken together, inhibition of NMDA receptors in the PFC does not seem to be enough to impair PPI per se but NMDA receptor mediated signalling in the PFC may be a key factor for the PPI-disruptive effects of global NMDA receptor inhibition. This indicates that targeting PFC NMDA receptor signalling may have potential as a treatment target for schizophrenia although further studies are needed to understand pharmacology and pathophysiological role of PFC NMDA receptors.
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