Nitric oxide synthase inhibitors attenuate phencyclidine-induced disruption of prepulse inhibition. 1998

J L Wiley
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298-0613, USA.

Glutamate stimulation of N-methyl-D-aspartate (NMDA) receptors results in release of nitric oxide which may mediate the effects of NMDA receptor stimulation and/or may result in feedback inhibition of the presynaptic neuron. Results of a previous study showed that nitric oxide synthase (NOS) inhibitors blocked dizocilpine-induced behavior in mice. In the present study, NOS inhibitors were tested in combination with phencyclidine (PCP), a drug which typically dose-dependently disrupts prepulse inhibition of the acoustic startle response in rats. Alone, NOS inhibitors and promoters do not affect prepulse inhibition; however, when tested in combination with PCP, the NOS inhibitors, L-NOARG, 7-nitroindazole and arcaine--but not the NR2B-selective polyamine site NMDA antagonist, eliprodil--attenuated PCP-induced disruption of prepulse inhibition of the acoustic startle response. These effects are similar to those produced by many atypical antipsychotics and suggests that this class of drugs should be investigated further for their potential utility as antipsychotics and as treatments for PCP abuse.

UI MeSH Term Description Entries
D007191 Indazoles A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES. Indazole
D007266 Inhibition, Psychological The interference with or prevention of a behavioral or verbal response even though the stimulus for that response is present; in psychoanalysis the unconscious restraining of an instinctual process. Inhibition (Psychology),Inhibition, Psychology,Psychological Inhibition,Inhibitions (Psychology),Inhibitions, Psychological,Inhibitions, Psychology,Psychological Inhibitions,Psychology Inhibition,Psychology Inhibitions
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
D010880 Piperidines A family of hexahydropyridines.
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
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
D001645 Biguanides Derivatives of biguanide (the structure formula HN(C(NH)NH2)2) that are primarily used as oral HYPOGLYCEMIC AGENTS for the treatment of DIABETES MELLITUS, TYPE 2 and PREDIABETES. Biguanide
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

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