Impaired limbic cortico-striatal structure and sustained visual attention in a rodent model of schizophrenia.
Samuel A Barnes, Stephen J Sawiak, Daniele Caprioli, Bianca Jupp, Guido Buonincontri, Adam C Mar, Michael K Harte, Paul C Fletcher, Trevor W Robbins, Jo C Neill, Jeffrey W Dalley
The international journal of neuropsychopharmacology October 31, 2014 DOI: 10.1093/ijnp/pyu010 via PubMed
Summary
AI-generated from the abstractSub-chronic exposure to the NMDA receptor antagonist phencyclidine (PCP) in rats produced localized reductions in grey matter density in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala, along with reduced cortical thickness in the insular cortex. PCP-treated rats also showed impaired sustained visual attention on a 5-choice serial reaction time task, especially under higher attentional load, but no significant effect on attentional filtering in an acoustic startle paradigm. These findings indicate that NMDA receptor antagonism can cause brain structural abnormalities in regions implicated in schizophrenia and dissociable attentional deficits.
Study at a glance
| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Phencyclidine (PCP) |
| Dose | 5mg/kg twice daily for 7 days |
| Duration | 7-day treatment |
| Keywords | 5-csrtt Pcp Vbm Anterior cingulate cortex Hippocampus |
| Key finding | Sub-chronic PCP treatment reduced grey matter density in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala, and impaired sustained visual attention under increased load. |
Abstract
N-methyl-d-aspartate receptor (NMDAR) dysfunction is thought to contribute to the pathophysiology of schizophrenia. Accordingly, NMDAR antagonists such as phencyclidine (PCP) are used widely in experimental animals to model cognitive impairment associated with this disorder. However, it is unclear whether PCP disrupts the structural integrity of brain areas relevant to the profile of cognitive impairment in schizophrenia. Here we used high-resolution magnetic resonance imaging and voxel-based morphometry to investigate structural alterations associated with sub-chronic PCP treatment in rats. Sub-chronic exposure of rats to PCP (5mg/kg twice daily for 7 days) impaired sustained visual attention on a 5-choice serial reaction time task, notably when the attentional load was increased. In contrast, sub-chronic PCP had no significant effect on the attentional filtering of a pre-pulse auditory stimulus in an acoustic startle paradigm. Voxel-based morphometry revealed significantly reduced grey matter density bilaterally in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala. PCP-treated rats also exhibited reduced cortical thickness in the insular cortex. These findings demonstrate that sub-chronic NMDA receptor antagonism is sufficient to produce highly-localized morphological abnormalities in brain areas implicated in the pathogenesis of schizophrenia. Furthermore, PCP exposure resulted in dissociable impairments in attentional function.