Synaptic biomarker reduction and impaired cognition in the sub-chronic PCP mouse model for schizophrenia.
Sub-chronic phencyclidine treatment (scPCP) provides a translational rat model for cognitive impairments associated with schizophrenia (CIAS). CIAS genetic risk factors may be more easily studied in mice however, CIAS associated biomarker changes are relatively unstudied in the scPCP mouse. To characterize deficits in object recognition memory and synaptic markers in frontal cortex and hippocampus of the scPCP mouse. Female c57bl6 mice received 10 daily injections of PCP (scPCP 10 mgkg, s.c.) or vehicle ( scPCP mice showed object memory deficits when distracted by removal from the arena, where they treated previously experienced objects as novel at test. scPCP significantly reduced PV expression in all regions and lower PSD95 levels in frontal cortex and ventral hippocampus. Levels of GAD67 and SNAP-25 were unchanged. We show for the first time that scPCP mice (a) can encode and retain object information, but that this memory is susceptible to distraction (b) display amnesia after distraction and (c) express reduced PV and PSD95 in frontal cortex and hippocampus. These data further support reductions in PV-dependent synaptic inhibition and NMDAR-dependent glutamatergic plasticity in CIAS and highlight the translational significance of the scPCP mouse.