A characterization of anxiolytic-like actions induced by the novel NMDA/glycine site antagonist, L-701,324. 1998

J Kotlinska, and S Liljequist
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.

The effects of the NMDA/glycine site antagonist, 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(1H)-quinolone (L-701,324), and the benzodiazepine receptor agonist, diazepam, were examined in the elevated plus-maze and in the Vogel's conflict test. Oral administration of L-701,324 caused a dose-dependent increase (2.5 and 5.0 mg/kg, -30 min) in the percent time spent in the open arms with no change in the total number of arm entries or in the percent entries into the open arms of the plus-maze. The same doses of L-701,324 increased punished responding in the Vogel's conflict test in a dose-dependent fashion, with no influence on unpunished drinking behavior. The anxiolytic-like effects of L-701,324 were obtained at doses which by themselves had no influence on the locomotor activity of the animals. Diazepam (2 mg/kg, i.p., -30 min) was slightly more effective than L-701,324 in the plus-maze situation, whereas the increase in punished drinking in the Vogel's test was of the same magnitude for both compounds. Our present results suggest that inhibition of NMDA receptor activity via a blockade of the NMDA/glycine-sensitive site at the NMDA receptor is accompanied by a reduction of anxiety-like behavior in both non-conditioned and conditioned conflict behavior situations.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
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
D001007 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS. Angst,Anxiousness,Hypervigilance,Nervousness,Social Anxiety,Anxieties, Social,Anxiety, Social,Social Anxieties
D014151 Anti-Anxiety Agents Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here. Anti-Anxiety Agent,Anti-Anxiety Drug,Anxiolytic,Anxiolytic Agent,Anxiolytic Agents,Tranquilizing Agents, Minor,Anti-Anxiety Drugs,Anti-Anxiety Effect,Anti-Anxiety Effects,Antianxiety Effect,Antianxiety Effects,Anxiolytic Effect,Anxiolytic Effects,Anxiolytics,Tranquillizing Agents, Minor,Agent, Anti-Anxiety,Agent, Anxiolytic,Agents, Anti-Anxiety,Agents, Anxiolytic,Agents, Minor Tranquilizing,Agents, Minor Tranquillizing,Anti Anxiety Agent,Anti Anxiety Agents,Anti Anxiety Drug,Anti Anxiety Drugs,Anti Anxiety Effect,Anti Anxiety Effects,Drug, Anti-Anxiety,Drugs, Anti-Anxiety,Effect, Anti-Anxiety,Effect, Antianxiety,Effect, Anxiolytic,Effects, Anti-Anxiety,Effects, Antianxiety,Effects, Anxiolytic,Minor Tranquilizing Agents,Minor Tranquillizing Agents
D015363 Quinolones A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID. Ketoquinoline,Ketoquinolines,Oxoquinoline,Oxoquinolines,Quinolinone,Quinolinones,Quinolone
D016194 Receptors, N-Methyl-D-Aspartate A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity. N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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