Post-weaning social isolation and subchronic NMDA glutamate receptor blockade: Effects on locomotor activity and GABA signaling in the rat suggest independent mechanisms

A “double hit” murine model for schizophrenia shows alterations in the structure and neurochemistry of the medial prefrontal cortex and the hippocampus

“…This is in accordance with other reports using different perinatal MK-801 treatments, which have consistently found transient lower body weights that normalized in adolescence or in adulthood (Stefani and Moghaddam, 2005;Su et al, 2011). The previous studies using dual animal models of schizophrenia, combining postweaning social isolation rearing and acute MK-801 treatment, did not explore changes in body weight (Ashby et al, 2010;Hickey et al, 2012).…”

“…Given the importance of altered neurodevelopment on the etiopathogenesis of schizophrenia, some of these models consist in experimental interventions during embryogenesis or early postnatal development. One of the most used of such models is the administration of N-methyl-D-aspartate (NMDA) receptor antagonists during the perinatal period, which produces certain cognitive and social impairments similar to those found in schizophrenia (Abdul-Monim et al, 2006;Beninger et al, 2002;Hickey et al, 2012;Rung et al, 2005). Perinatal NMDA receptor antagonist administration also reduces GABAergic neurotransmission and the number of parvalbumin expressing neurons in the PFC and the hippocampus in adulthood (Rotaru et al, 2012).…”

“…A recent report has tested the hypothesis that a "double-hit" model combining MK-801 administration during adulthood and postweaning social isolation rearing of Sprague-Dawley rats, produces greater behavioral and neurochemical effects than either insult alone, with limited results (Hickey et al, 2012). In the present study, we have developed a similar "double hit" model in Lister Hooded rats, in order to find whether the combination of an earlier injection of MK-801, at postnatal day 7 (P7), which may alter different neurodevelopmental processes, and a postweaning social isolation rearing reproduces some of the structural and molecular changes found in the mPFC and the hippocampus of schizophrenic patients, particularly in their inhibitory networks.…”

Development and characterization of chronic animal models of schizophrenia

“…certain combinations of the above mentioned models to investigate the hypothesis that these manipulations can enhance the reliability of the schizophrenia model [16,[86][87][88]. One of the most popular methods is the gene-enviromental interactions, including ventral hippocampal lesion with social isolation which produced an additive effect on locomotor activity and morphological changes in the prefrontal cortex and NAcc [89,90].…”

“…Cessation of treatment in adult or juvenile rodents did not cause gross changes in motor activity, while early postnatal treatment was effective in this respect [48,50,130,207]. Beninger's laboratory investigated the effects of subchronic MK-801 treatment and postweaning social isolation on motor activity [86,87,208].…”