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The nitric oxide synthase inhibitor, L-NAME, block phencyclidine-induced disruption of prepulse inhibition in mice. 2001

D Klamer, and J A Engel, and L Svensson
Department of Pharmacology, Göteborg University, Sweden.

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.

UI MeSH Term Description Entries
D008297 Male Males
D010622 Phencyclidine A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust. 1-(1-Phenylcyclohexyl)piperidine,Angel Dust,CL-395,GP-121,Phencyclidine Hydrobromide,Phencyclidine Hydrochloride,Sernyl,Serylan,CL 395,CL395,Dust, Angel,GP 121,GP121
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006213 Hallucinogens Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. Hallucinogen,Hallucinogenic Agent,Hallucinogenic Drug,Hallucinogenic Substance,Psychedelic,Psychedelic Agent,Psychedelic Agents,Psychotomimetic Agent,Psychotomimetic Agents,Hallucinogenic Agents,Hallucinogenic Drugs,Hallucinogenic Substances,Psychedelics,Agent, Hallucinogenic,Agent, Psychedelic,Agent, Psychotomimetic,Agents, Hallucinogenic,Agents, Psychedelic,Agents, Psychotomimetic,Drug, Hallucinogenic,Drugs, Hallucinogenic,Substance, Hallucinogenic,Substances, Hallucinogenic
D000161 Acoustic Stimulation Use of sound to elicit a response in the nervous system. Auditory Stimulation,Stimulation, Acoustic,Stimulation, Auditory
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013216 Reflex, Startle A complex involuntary response to an unexpected strong stimulus. The reaction involves physical movement away from the stimulus, MUSCLE CONTRACTION and limb flexion, BLINKING, and changes in HEART RATE, BLOOD PRESSURE, and RESPIRATION. Startle Reaction,Acoustic Startle Reflex,Reflex, Moro,Startle Response,Moro Reflex,Reaction, Startle,Reactions, Startle,Reflex, Acoustic Startle,Response, Startle,Responses, Startle,Startle Reactions,Startle Reflex,Startle Reflex, Acoustic,Startle Responses
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D052247 Nitric Oxide Synthase Type II A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES. INOS Enzyme,Inducible NOS Protein,Inducible Nitric Oxide Synthase,NOS-II,Nitric Oxide Synthase II,Nitric Oxide Synthase, Type II,NOS II

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