Neonatal ventral hippocampus lesions disrupt extra-dimensional shift and alter dendritic spine density in the medial prefrontal cortex of juvenile rats

Recent data showed that neonatal ventral hippocampus (VH) lesions, an approach used to model schizophrenia symptoms in rodents, produce premature deficits of working memory believed to be associated with early medial prefrontal cortex (mPFC) maldevelopment. This experiment expands the investigation of mPFC integrity in juvenile rats with neonatal VH lesions by assessing behavioral flexibility and dendritic spine density. Sixteen Sprague-Dawley male pups received bilateral microinjections of ibotenic acid in the VH or SHAM surgery on postnatal day (PND) 6. On PND 29 and 30, rats were subjected to a spatial shift task in a cross-maze; an attentional set-shifting task was then administered on two consecutive days, between PND 33 and PND 35. Rats were sacrificed at PND 36 and dendritic spine density in the mPFC was assessed using Golgi-Cox staining procedure. Results revealed impaired extra-dimensional shift in VH-lesioned rats and inconsistent reversal discrimination outcomes. Although lesioned animals displayed intact performance in the spatial shift, rates of perseverative responses were higher than normal in this task. Neonatal VH damage resulted in lower dendritic spine density in the mPFC than measured in control brains; however, no significant correlation was found between this outcome and behavioral data. Juvenile morphological and cognitive perturbations are consistent with the early emergence of mPFC anomalies following neonatal VH lesions. Results are discussed in relation with potential common mechanisms linking pre- and post-pubertal onsets of behavioral dysfunction.     

Schizophrenia-like syndrome inducing agent phencyclidine failed to impair memory for temporal order in rats

Although subchronic phencyclidine (PCP) administration is recognized as a probative method to model schizophrenia-like symptoms in animals, only a few sets of data support the hypothesis of a cognitive prefrontal cortex (PFc) dysfunction in PCP-treated monkeys and rodents. Two experiments were here conducted to further test the integrity of prefrontal function in two versions of a memory for temporal order (MTO) task administered to rats. Original versions of this task elaborated by Kesner repeatedly yielded moderate to severe performance deficits in PFc lesioned rats. MTO assessment in an eight-arm radial maze consisted in a recency discrimination between two arms previously explored in the context of sequential forced choices. In Experiment 1, 16 naive Long-Evans rats were pre-trained on a variable version of the MTO task involving randomly re-mixed sequences until they reached a group criterion. Then, rats were treated daily for 21 days with PCP (10mg/kg) or saline vehicle and were tested on the same task approximately 20 h after an injection. The performance of the groups did not differ. In Experiment 2, 16 naive Long-Evans rats untrained prior to treatment received 27 daily injections of either PCP (10mg/kg) or saline vehicle and were tested, 20 h after each injection, on a constant version of the MTO task. This time, a fixed set of four sequences of successive arm entries was repeated within each daily session as well as across days. Again, prolonged PCP exposure failed to impair discrimination of temporal order despite the stability of sequential information over time. These negative results are not consistent with long-lasting hypofrontality, a major landmark of human schizophrenia, in the PCP rat model.