title: Neonatal phencyclidine administration and post-weaning social isolation as a dual-hit model of 'schizophrenia-like' behaviour in the rat.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Philip L R
authors.initials: PL
authors.lastname: Gaskin
authors.forename: Stephen P H
authors.initials: SP
authors.lastname: Alexander
authors.forename: Kevin C F
authors.initials: KC
authors.lastname: Fone
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D004644:Emotions; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D046352:Freezing Reaction, Cataleptic; D008297:Male; D008568:Memory; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D010364:Pattern Recognition, Visual; D010622:Phencyclidine / Q000008:administration & dosage*; D065808:Prepulse Inhibition; D051381:Rats; D012559:Schizophrenia / Q000503:physiopathology*; D012934:Social Isolation
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010622:Phencyclidine