ArticlePsychopharmacology2021
Neonatal phencyclidine and social isolation in the rat: effects of clozapine on locomotor activity, social recognition, prepulse inhibition, and executive functions deficits.
Article in Psychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- Evaluating neurochemical changes and associated locomotor activity in a double hit schizophrenia model.IBRO neuroscience reports · 2026Article
- Altered lipid peroxidation, perineuronal net and oligodendrocyte markers in the frontal cortex of a dual-hit neurodevelopmental model support its relevance to schizophrenia.Frontiers in cellular neuroscience · 2026Article
- GABAergic and inflammatory changes in the frontal cortex following neonatal PCP plus isolation rearing, as a dual-hit neurodevelopmental model for schizophrenia.Molecular neurobiology · 2024Article
- Advances in the study of phencyclidine-induced schizophrenia-like animal models and the underlying neural mechanisms.Schizophrenia (Heidelberg, Germany) · 2024Review
- Investigating the Robustness of a Rodent "Double Hit" (Post-Weaning Social Isolation and NMDA Receptor Antagonist) Model as an Animal Model for Schizophrenia: A Systematic Review.Brain sciences · 2023Review
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5 authors at 1 institution in 1 country.
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Abstract
rationaleThere is a need to develop animal models of schizophrenia-like behaviors that have both construct and predictive validity. Recently, a neonatal phencyclidine (PCP) and post-weaning social isolation dual-hit model was developed; however, its face and predictive validities need to be further investigated.
objectiveThe aims of this study were to extend the characterization of the behavioral changes occurring in the neonatal PCP and post-weaning social isolation dual-hit rat model and to evaluate the effects of chronic treatment with clozapine on signs related to schizophrenia.
methodsMale Wistar rat pups were treated with PCP (10 mg/kg s.c.) on postnatal days (PND) 7, 9, and 11. Starting from weaning, neonatal PCP-treated rat pups were socially isolated, while control saline-treated rats were group housed. At adulthood, rats were assessed using behavioral tasks evaluating locomotor activity, social recognition, prepulse inhibition, and reversal learning. Clozapine (3 mg/kg i.p.) was administered daily starting from a week before behavioral tests and until the end of the study.
resultsNeonatal PCP-treated and post-weaning social isolated (PCP-SI) rats displayed persistent and robust locomotor hyperactivity as well as social recognition impairment. The latter could not be explained by variations in the motivation to interact with a juvenile rat. Weak-to-moderate deficits in prepulse inhibition and reversal learning were also observed. Chronic treatment with clozapine attenuated the observed locomotor hyperactivity and social recognition deficits.
conclusionThe PCP-SI model presents enduring and robust deficits (hyperactivity and social recognition impairment) associated with positive symptoms and cognitive/social deficits of schizophrenia, respectively. These deficits are normalized by chronic treatment with clozapine, thereby confirming the predictive validity of this animal model.
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