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The amino acid l-lysine blocks the disruptive effect of phencyclidine on prepulse inhibition in mice

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Abstract

Rationale

The cognitive and attentional deficits observed in schizophrenic patients are now considered central to the pathophysiology of the disorder. These deficits include an inability to filter sensory input as measured by, e.g., prepulse inhibition (PPI) reflex. Administration of phencyclidine (PCP), a drug that can induce a schizophrenia-like psychosis in humans, disrupts PPI in experimental animals. In rodents, this PCP-induced deficit can be blocked by pretreatment with nitric oxide (NO) synthase inhibitors. This suggests that some of the behavioral effects of PCP are mediated via NO. The substrate for in vivo NO production is l-arginine, and active transport of l-arginine via the cationic amino acid transporter may serve as a regulatory mechanism in NO production.

Objectives

The aim of the present study was to study the effects of l-arginine transport inhibition, using acute and repeated l-lysine treatment, on PCP-induced disruption of PPI in mice.

Results

Subchronic, and to some extent acute, pretreatment with l-lysine blocked a PCP-induced deficit in PPI without affecting basal PPI.

Conclusions

l-lysine has been shown to block l-arginine transport in vitro, most likely via a competitive blockade and down regulation of cationic amino acid transporters. However, the importance of l-arginine transport as a regulatory mechanism in NO production in vivo is still not clear. The present results lend further support to the notion that some of the effects of PCP in the central nervous system are mediated via NO and that l-arginine transport may play a role in the regulation of NO production in the brain.

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Acknowledgments

This study was supported by grants from the Swedish Medical Research Council (4247), the Theodore and Vada Stanley Foundation, Magnus Bergvalls Stiftelse, Stiftelsen Clas Groschinskys Minnesfond, Göteborgs Läkaresällskap, Wilhelm och Martina Lundgrens Vetenskapsfond, Stiftelsen Bengt Dahréns fond, the Swedish Society of Medicine, Åke Wibergs Stiftelse, Adlerbertska Forskningsstiftelsen, Fredrik och Ingrid Thurings Stiftelse, Åhlén-Stiftelsen and Svenska Lundbeckstiftelsen.

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  1. Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, POB 431, 405 30, Göteborg, Sweden

    Erik Pålsson, Kim Fejgin, Caroline Wass, Jörgen A. Engel, Lennart Svensson & Daniel Klamer

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  1. Erik Pålsson
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  2. Kim Fejgin
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  3. Caroline Wass
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  4. Jörgen A. Engel
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  5. Lennart Svensson
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  6. Daniel Klamer
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Correspondence to Daniel Klamer.

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Pålsson, E., Fejgin, K., Wass, C. et al. The amino acid l-lysine blocks the disruptive effect of phencyclidine on prepulse inhibition in mice. Psychopharmacology 192, 9–15 (2007). https://doi.org/10.1007/s00213-006-0683-x

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  • DOI: https://doi.org/10.1007/s00213-006-0683-x

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