The nitric oxide synthase inhibitor, L-NAME, block phencyclidine-induced disruption of prepulse inhibition in mice.
BACKGROUND
Schizophrenia is a major public health problem that affects approximately 1% of the population worldwide. Schizophrenia-like syndromes can be induced in humans by phencyclidine (PCP), a drug with marked psychomimetic properties. Recent studies show that the behavioural and biochemical effects of PCP in rats are blocked by nitric oxide synthase (NOS) inhibitors, suggesting that NO plays an important role in the pharmacological effects of PCP.


OBJECTIVE
The aim of this study was to investigate if PCP-induced disruption of prepulse inhibition of acoustic startle could be blocked by the NOS inhibitor, L-NAME, in mice.


RESULTS
The present study shows that PCP readily disrupts prepulse inhibition in mice normally without affecting pulse-alone trials. Furthermore, L-NAME blocked the PCP-induced disruption of prepulse inhibition in a dose-related manner.


CONCLUSIONS
The PCP-induced disruption of prepulse inhibition and the ability of L-NAME to block this effect in both rats and mice suggest that this is a general and not a species-specific effect. The results of the present study further suggest that PCP exerts at least some of its actions in the central nervous system by a NO-dependent mechanism.
Klamer
D
D
Department of Pharmacology, Göteborg University, Sweden.
Engel
J A
JA
Svensson
L
L
D000161:Acoustic Stimulation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006213:Hallucinogens / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010622:Phencyclidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013216:Reflex, Startle / Q000187:drug effects*
D004791:Enzyme Inhibitors; D006213:Hallucinogens; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D010622:Phencyclidine; D019331:NG-Nitroarginine Methyl Ester