title: Information processing deficits and nitric oxide signalling in the phencyclidine model of schizophrenia.
abstract: BACKGROUND
  Schizophrenia-like cognitive deficits induced by phencyclidine (PCP), a drug commonly used to model schizophrenia in experimental animals, are attenuated by nitric oxide (NO) synthase inhibitors. Furthermore, PCP increases NO levels and sGC/cGMP signalling in the prefrontal cortex in rodents. Hence, a cortical NO/sGC/cGMP signalling pathway may constitute a target for novel pharmacological therapies in schizophrenia.
  
  
  OBJECTIVE
  The objective of this study was to further investigate the role of NO signalling for a PCP-induced deficit in pre-attentive information processing.
  
  
  METHODS
  Male Sprague-Dawley rats were surgically implanted with NO-selective amperometric microsensors aimed at the prefrontal cortex, ventral hippocampus or nucleus accumbens, and NO levels and prepulse inhibition (PPI) were simultaneously assessed.
  
  
  RESULTS
  PCP treatment increased NO levels in the prefrontal cortex and ventral hippocampus, but not in the nucleus accumbens. The increase in NO levels was not temporally correlated to the deficit in PPI induced by PCP. Furthermore, pretreatment with the neuronal NO synthase inhibitor N-propyl-L-arginine dose-dependently attenuated both the increase in prefrontal cortex NO levels and the deficit in PPI.
  
  
  CONCLUSIONS
  These findings support a demonstrated role of NO in the behavioural and neurochemical effects of PCP. Furthermore, this effect is brain region-specific and mainly involves the neuronal isoform of NOS. However, a temporal correlation between a PCP-induced disruption of PPI and an increase in prefrontal cortex NO levels was not demonstrated, suggesting that the interaction between PCP and the NO system is more complex than previously thought.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, POB 431, 405 30, Gothenburg, Sweden. erik.palsson@pharm.gu.se
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
authors.forename: John
authors.initials: J
authors.lastname: Lowry
authors.forename: Daniel
authors.initials: D
authors.lastname: Klamer
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D055664:Electrochemical Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017736:Ion-Selective Electrodes; D008297:Male; D009433:Neural Inhibition; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010622:Phencyclidine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle; D012559:Schizophrenia / Q000378:metabolism*; D012565:Schizophrenic Psychology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D010622:Phencyclidine
references.citation: Behav Brain Res. 2006 Nov 1;174(1):49-55
references.pmid: 16935357
references.citation: Psychopharmacology (Berl). 2001 Jul;156(2-3):117-54
references.pmid: 11549216
references.citation: Psychopharmacology (Berl). 2008 Aug;199(3):331-88
references.pmid: 18568339
references.citation: Psychopharmacology (Berl). 2001 Jul;156(2-3):182-6
references.pmid: 11549221
references.citation: Neuropsychopharmacology. 2008 Jul;33(8):1874-83
references.pmid: 17895915
references.citation: Psychopharmacology (Berl). 2005 May;179(2):479-88
references.pmid: 15619121
references.citation: Behav Brain Res. 2005 Jun 3;161(1):60-8
references.pmid: 15904710
references.citation: Analyst. 2009 Oct;134(10):2012-20
references.pmid: 19768208
references.citation: Neurochem Int. 1998 Jul;33(1):29-34
references.pmid: 9694039
references.citation: Behav Brain Res. 2009 Jun 8;200(1):113-6
references.pmid: 19166879
references.citation: J Neurosci. 1997 Mar 1;17(5):1769-75
references.pmid: 9030635
references.citation: J Neurosci. 1998 Jul 15;18(14):5545-54
references.pmid: 9651235
references.citation: Neurochem Res. 2001 Sep;26(8-9):1069-78
references.pmid: 11699933
references.citation: Neuron. 2008 Nov 26;60(4):642-56
references.pmid: 19038221
references.citation: Mol Cell Biochem. 2010 Jan;334(1-2):221-32
references.pmid: 20012469
references.citation: J Neurosci. 2007 Oct 24;27(43):11496-500
references.pmid: 17959792
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14515-20
references.pmid: 16176986
references.citation: J Neurochem. 2009 Dec;111(6):1457-65
references.pmid: 19799710
references.citation: Nitric Oxide. 2009 Sep;21(2):92-103
references.pmid: 19602444
references.citation: Br J Pharmacol. 2000 Jul;130(5):1005-12
references.pmid: 10882384
references.citation: Am J Psychiatry. 2009 Apr;166(4):434-41
references.pmid: 19255043
references.citation: Schizophr Res. 2001 Apr 15;49(1-2):171-8
references.pmid: 11343875
references.citation: Prog Neurobiol. 2005 Jun;76(2):126-52
references.pmid: 16115721
references.citation: Life Sci. 1988;42(18):1713-23
references.pmid: 2452334
references.citation: Anal Bioanal Chem. 2005 Feb;381(4):964-71
references.pmid: 15726338
references.citation: Psychopharmacology (Berl). 2004 Nov;176(3-4):440-50
references.pmid: 15173930
references.citation: Neuroreport. 2004 Mar 22;15(4):677-80
references.pmid: 15094474
references.citation: J Neurocytol. 2001 Aug;30(8):661-70
references.pmid: 12118154
references.citation: Neuroreport. 1998 Sep 14;9(13):2985-8
references.pmid: 9804302
references.citation: Psychopharmacology (Berl). 2009 Jan;202(1-3):411-7
references.pmid: 18716761
references.citation: Neuropsychopharmacology. 2009 Jun;34(7):1673-84
references.pmid: 19145229
references.citation: Psychopharmacology (Berl). 1997 May;131(2):167-73
references.pmid: 9201805
references.citation: J Comp Neurol. 2001 Dec 24;441(4):288-301
references.pmid: 11745651
references.citation: J Physiol. 2006 Dec 1;577(Pt 2):549-67
references.pmid: 16973697
references.citation: Neurosci Lett. 1991 Jul 22;128(2):191-4
references.pmid: 1834964
references.citation: Mol Psychiatry. 2006 Mar;11(3):286-300
references.pmid: 16389274
references.citation: Biochem J. 2009 Apr 15;419(2):411-8
references.pmid: 19152507
references.citation: Histol Histopathol. 1998 Oct;13(4):1243-52
references.pmid: 9810515
references.citation: Psychopharmacology (Berl). 2001 May;155(3):299-309
references.pmid: 11432693
references.citation: Pharmacol Biochem Behav. 2007 Nov;88(1):73-81
references.pmid: 17698179
references.citation: Neuropharmacology. 2009 Sep;57(3):193-200
references.pmid: 19523965
references.citation: Methods Find Exp Clin Pharmacol. 2006 Mar;28(2):95-9
references.pmid: 16636719
references.citation: Analyst. 2003 Jun;128(6):700-5
references.pmid: 12866891
references.citation: Eur J Pharmacol. 2004 Oct 25;503(1-3):103-7
references.pmid: 15496304
references.citation: Br J Pharmacol. 2000 Jun;130(3):575-80
references.pmid: 10821785
references.citation: Synapse. 2009 Dec;63(12):1083-8
references.pmid: 19642219
references.citation: J Neurosci Methods. 1997 Feb;71(2):177-82
references.pmid: 9128153
references.citation: Eur J Neurosci. 2004 Dec;20(12):3424-32
references.pmid: 15610175
references.citation: Basic Clin Pharmacol Toxicol. 2004 Feb;94(2):65-72
references.pmid: 14748849
references.citation: Neuropsychopharmacology. 1998 Jul;19(1):86-94
references.pmid: 9608580
references.citation: Neuropharmacology. 2004 Mar;46(4):480-9
references.pmid: 14975671
references.citation: Clin Neuropharmacol. 1997 Aug;20(4):357-63
references.pmid: 9260734