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Abstract

Considering data on the possible glutamatergic nature of the pathogenesis of schizophrenia, we attempted to model cognitive derangements in animals by chronic blockade of NMDA glutamate receptors. Wistar rats received daily s.c. injections of the non-competitive NMDA glutamate receptor antagonist MK-801 (0.05 mg/kg) from days 7 to day 49 of postnatal life. One day after the antagonist injections given on days 27 and 28 of life, animals of the experimental group showed decreased levels of spontaneous movement and orientational-investigative activity as compared with controls, where there was no change in the elevated locomotor reaction produced in response to the direct action of MK-801. These animals showed decreases in the level of anxiety (on day 40 of life) and derangement in spatial learning with food reinforcement (days 50-54 of life). It is suggested that early neonatal blockade of NMDA glutamate receptors leads to the development in animals of disturbances to situational perception and assessment of incoming sensory information.

Reduced d-serine levels drive enhanced non-ionotropic NMDA receptor signaling and destabilization of dendritic spines in a mouse model for studying schizophrenia

“…Furthermore, there is evidence of increased d -amino acid oxidase expression in schizophrenia ( Madeira et al, 2008 ), which similarly would contribute to lower d -serine and subsequent NMDAR hypofunction. Importantly, animal studies that mimic NMDAR hypofunction by reducing ion flux or co-agonist binding show cognitive deficits and decreased spine density ( Barnes et al, 2014 ; Basu et al, 2009 ; Labrie et al, 2009 ; Latysheva and Raevskii, 2003 ; Schobel et al, 2013 ; Wu et al, 2016 ).…”