Involvement of NMDA receptor complex in the anxiolytic-like effects of chlordiazepoxide in mice

In the present study, we demonstrated that low, ineffective doses of N -methyl- d -aspartic acid (NMDA) receptor antagonists [competitive NMDA antagonist, CGP 37849, at 0.312 mg/kg intraperitoneally (i.p.), antagonist of the glycine B sites, L-701,324, at 2 mg/kg i.p., partial agonist of glycine B s...

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Bibliographic Details
Published in:Journal of Neural Transmission 2011-06, Vol.118 (6), p.857-864
Main Authors: Poleszak, Ewa, Socała, Katarzyna, Szopa, Aleksandra, Wróbel, Andrzej, Szewczyk, Bernadeta, Kasperek, Regina, Blicharska, Eliza, Nowak, Gabriel, Wlaź, Piotr
Format: Article
Language:English
Subjects:
Animals
Anti-Anxiety Agents - pharmacology
Anxiety Disorders - drug therapy
Anxiety Disorders - metabolism
Anxiety Disorders - physiopathology
Basic Neurosciences
Basic Neurosciences, Genetics and Immunology - Original
Chlordiazepoxide - pharmacology
GABA Modulators - pharmacology
gamma-Aminobutyric Acid - physiology
Genetics and Immunology - Original Article
Glutamic Acid - physiology
Male
Medicine
Medicine & Public Health
Mice
Neurology
Neurosciences
Psychiatry
Receptors, N-Methyl-D-Aspartate - agonists
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - physiology
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Summary:In the present study, we demonstrated that low, ineffective doses of N -methyl- d -aspartic acid (NMDA) receptor antagonists [competitive NMDA antagonist, CGP 37849, at 0.312 mg/kg intraperitoneally (i.p.), antagonist of the glycine B sites, L-701,324, at 2 mg/kg i.p., partial agonist of glycine B sites, d -cycloserine, at 2.5 mg/kg i.p.] administered jointly with an ineffective dose of the benzodiazepine, chlordiazepoxide (CDP, 2.5 mg/kg i.p.), significantly increased the percentage of time spent in the open arms of the elevated plus-maze (index of anxiolytic effect). Furthermore, CDP-induced anxiolytic-like activity (5 mg/kg i.p.) was antagonized by NMDA (75 mg/kg i.p.) and by an agonist of glycine B sites of the NMDA receptor complex, d -serine [100 nmol/mouse intracerebroventricularly (i.c.v.)]. The present study showed a positive interaction between γ-aminobutyric acid (GABA) and glutamate neurotransmission in the anxiolytic-like activity in the elevated plus-maze test in mice and this activity seems to particularly involve the NMDA receptors.
ISSN:0300-9564
1435-1463
DOI:10.1007/s00702-011-0585-x