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Neonatal phencyclidine administration and post-weaning social isolation as a dual-hit model of 'schizophrenia-like' behaviour in the rat

Gaskin, Philip LR; Fone, Kevin ; Alexander, Stephen

Authors

Philip LR Gaskin

Kevin Fone

Stephen Alexander



Abstract

Rationale: Schizophrenia is a debilitating disorder comprising positive, negative and cognitive deficits with a poorly defined neurobiological aetiology; therefore, animal models with greater translational reliability are essential to develop improved therapies. Objectives: This study combines two developmental challenges in rats, neonatal phencyclidine (PCP) injection and subsequent rearing in social isolation from weaning, to attempt to produce more robust behavioural deficits with greater translational relevance to schizophrenia than either challenge alone. Methods: Forty-two male Lister-hooded rat pups received the N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine (PCP, 10 mg/kg, s.c.), or vehicle on post-natal day (PND) 7, 9 and 11 and were weaned on PND 23 into group housing (saline-treated n∈=∈11 or PCP-treated n∈=∈10) or isolation (saline n∈=∈10 or PCP n∈=∈11). Six weeks post-weaning, novelty- and PCP-induced (3.2 mg/kg) locomotor activity, novel object discrimination, prepulse inhibition of acoustic startle and contextual memory in a conditioned emotion response (CER) were recorded. Results: Isolation rearing alone significantly elevated baseline locomotor activity and induced visual recognition memory impairment in novel object discrimination. Neonatal PCP treatment did not induce locomotor sensitisation to a subsequent acute PCP injection, but it impaired prepulse inhibition when combined with isolation rearing. CER freezing behaviour was significantly reduced by isolation rearing but an even greater effect occurred when combined with neonatal PCP treatment. Conclusions: Neonatal PCP and isolation rearing both produce behavioural deficits in adult rats, but combined treatment caused a wider range of more severe cognitive impairments, providing a more comprehensive preclinical model to determine the neurobiological aetiology of schizophrenia than either treatment alone. © 2014 Springer-Verlag Berlin Heidelberg.

Journal Article Type Article
Publication Date 2014-06
Journal Psychopharmacology
Print ISSN 0033-3158
Electronic ISSN 1432-2072
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 231
Issue 12
Pages 2533-2545
APA6 Citation Gaskin, P. L., Fone, K., & Alexander, S. (2014). Neonatal phencyclidine administration and post-weaning social isolation as a dual-hit model of 'schizophrenia-like' behaviour in the rat. Psychopharmacology, 231(12), 2533-2545. https://doi.org/10.1007/s00213-013-3424-y
DOI https://doi.org/10.1007/s00213-013-3424-y
Keywords Pharmacology
Publisher URL https://link.springer.com/article/10.1007%2Fs00213-013-3424-y
PMID 24402141
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