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3235328 
Journal Article 
The amino acid l-lysine blocks the disruptive effect of phencyclidine on prepulse inhibition in mice 
Palsson, E; Fejgin, Kim; Wass, C; Engel, JA; Svensson, L; Klamer, D 
2007 
1 
Psychopharmacology
ISSN: 0033-3158
EISSN: 1432-2072 
192 
1 
9-15 
WOS:000246100300002 
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. 
nitric oxide; prepulse inhibition; schizophrenia; phencyclidine; mice; l-arginine; l-lysine