Palsson, Erik and Lowry, John P. and Klamer, Daniel (2010) Information processing deficits and nitric oxide signalling in the phencyclidine model of schizophrenia. Psychopharmacology, 212 (4). pp. 643-651. ISSN 0033-3158

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Abstract

Rationale 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. Objectives The objective of this study was to further investigate the role of NO signalling for a PCP-induced deficit in pre-attentive information processing. Materials and 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.

Item Type:	Article
Keywords:	Prepulse inhibition; Rat; Nitric oxide; Schizophrenia; Voltammetry; Phencyclidine; Prefrontal cortex; Nitric oxide synthase; NMDA receptor;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	8025
Identification Number:	https://doi.org/10.1007/s00213-010-1992-7
Depositing User:	John Lowry
Date Deposited:	13 Mar 2017 17:02
Journal or Publication Title:	Psychopharmacology
Publisher:	Springer Verlag
Refereed:	Yes
URI:	http://link.springer.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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