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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Phencyclidine (PCP) |
| Dose | 5 mg/kg twice daily for 7 days |
| Duration | 7-day treatment |
| Measures | 5-choice serial reaction time task, acoustic startle paradigm, voxel-based morphometry |
| Keywords | 5-csrtt Pcp Vbm Anterior cingulate cortex Hippocampus |
| Key findings | 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.