title: Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats.
abstract: BACKGROUND
  We have previously demonstrated that subchronic (five daily administrations of 2.6 mg/kg PCP) and chronic intermittent administration of 2.6 mg/kg PCP to rats produces hypofrontality and other neurochemical changes akin to schizophrenia pathology (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003).
  
  
  OBJECTIVE
  We sought to determine whether behavioral alterations related to discrete aspects of schizophrenia are also induced by these PCP treatment regimes.
  
  
  METHODS
  Following administration of vehicle or PCP according to the protocols described above, rats were assessed for attentional set shifting ability, prepulse inhibition (PPI), or social interaction and the locomotor response to a challenge dose of amphetamine.
  
  
  RESULTS
  Ability to shift attentional set was impaired 72 h after the last PCP administration following the subchronic and chronic intermittent treatment regimes. PPI was disrupted after each acute administration of PCP in animals under the subchronic treatment regime. However, PPI deficits were not sustained 72 h after the last of five daily administrations. In subchronic and chronic PCP treated animals, no change was found in social interaction behavior, and there was little change in baseline or amphetamine-stimulated locomotor activity, employed as an indicator of dopaminergic hyperfunction.
  
  
  CONCLUSIONS
  The temporally distinct behavioral effects of these PCP treatment regimes suggest that PPI deficits relate directly to acute NMDA receptor antagonism, whereas the more enduring set shifting deficits relate to the longer term consequences of NMDA receptor blockade. Therefore, these subchronic and chronic PCP treatment regimes produce hypofrontality (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003) and associated prefrontal cortex-dependent deficits in behavioral flexibility which mirror core deficits in schizophrenia.
authors.affiliation: Psychiatric Research Institute of Neuroscience in Glasgow (PsyRING), University of Glasgow, Glasgow, G12 8QQ, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Egerton
authors.forename: Lee
authors.initials: L
authors.lastname: Reid
authors.forename: Sandie
authors.initials: S
authors.lastname: McGregor
authors.forename: Susan M
authors.initials: SM
authors.lastname: Cochran
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
authors.forename: Judith A
authors.initials: JA
authors.lastname: Pratt
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003072:Cognition Disorders / Q000139:chemically induced / Q000503:physiopathology; D004192:Discrimination, Psychological / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D005625:Frontal Lobe / Q000502:physiology; D006213:Hallucinogens / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced / Q000523:psychology; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D013216:Reflex, Startle / Q000187:drug effects*; D012565:Schizophrenic Psychology; D012919:Social Behavior
chemical_list: D000697:Central Nervous System Stimulants; D006213:Hallucinogens; D000661:Amphetamine; D010622:Phencyclidine; D004298:Dopamine