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

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.

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

• Journal Article Type: Article
• Acceptance Date: Dec 16, 2013
• Online Publication Date: Jan 9, 2014
• Publication Date: 2014-06
• Deposit Date: Sep 3, 2018
• Journal: Psychopharmacology
• Print ISSN: 0033-3158
• Electronic ISSN: 1432-2072
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 231
• Issue: 12
• Pages: 2533-2545
• DOI: https://doi.org/10.1007/s00213-013-3424-y
• Keywords: Pharmacology
• Public URL: https://nottingham-repository.worktribe.com/output/1097334
• Publisher URL: https://link.springer.com/article/10.1007%2Fs00213-013-3424-y
• PMID: 24402141