Information processing deficits and nitric oxide signalling in the phencyclidine model of schizophrenia.
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.
Pålsson
Erik
E
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
Lowry
John
J
Klamer
Daniel
D
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
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D010622:Phencyclidine
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