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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Amino Acid Transport Systems

Basic

metabolism

Amino Acids

administration & dosage

pharmacology

Animals

Arginine

metabolism

Behavior

Animal

drug effects

Biological Transport

drug effects

Disease Models

Animal

Dose-Response Relationship

Drug

Down-Regulation

drug effects

Hallucinogens

antagonists & inhibitors

pharmacology

Lysine

administration & dosage

pharmacology

Male

Mice

Nitric Oxide

biosynthesis

metabolism

Phencyclidine

antagonists & inhibitors

pharmacology

Reflex

drug effects

Schizophrenia

Startle Reaction

drug effects

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)