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

Poleszak E, Socała K, Szopa A, Wróbel A, Szewczyk B, Kasperek R, Blicharska E, Nowak G, Wlaź P - J Neural Transm (Vienna) (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland. ewa.poleszak@umlub.pl

ABSTRACT
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.

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Effect of joint administration of CGP 37849 and chlordiazepoxide (CDP) in the elevated plus-maze procedure in mice [the percentage of the time spent in the open arms (a), and the percentage of the open arms entries (b)]. CGP 37849 and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 8 mice per group) *p < 0.05 versus CGP 37849, ^p < 0.001 versus CDP, #p < 0.05 versus control (vehicle-treated group) (Bonferroni’s test)
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Fig1: Effect of joint administration of CGP 37849 and chlordiazepoxide (CDP) in the elevated plus-maze procedure in mice [the percentage of the time spent in the open arms (a), and the percentage of the open arms entries (b)]. CGP 37849 and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 8 mice per group) *p < 0.05 versus CGP 37849, ^p < 0.001 versus CDP, #p < 0.05 versus control (vehicle-treated group) (Bonferroni’s test)

Mentions: Chlordiazepoxide administered at a dose of 0.5 mg/kg or CGP 37849 administered at a dose of 0.312 mg/kg, both given alone, did not change the percentage of the time spent and also entries into the open arms with the exception of CDP, which significantly increased this latter measure (Fig. 1). The joint administration of CDP and CGP 37849 significantly increased the percentage of the time spent in the open arms (Fig. 1a) and enhanced the number of entries into open arms (Fig. 1b). A two-way ANOVA demonstrated lack of effect of CDP [F(1, 28) = 1.91, p = 0.1777], significant effect of CGP 37849 [F(1, 28) = 26.38, p < 0.0001] and significant interaction [F(1, 28) = 8.02, p = 0.0085] in the time spent in open arms, while a significant effect of CDP [F(1, 28) = 15.301, p = 0.0005], no effect of CGP 37849 [F(1, 28) = 2.93, p = 0.09882] and no interaction [F(1, 28) = 0.0, p = 0.9492] in the open arm entries.Fig. 1


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

Poleszak E, Socała K, Szopa A, Wróbel A, Szewczyk B, Kasperek R, Blicharska E, Nowak G, Wlaź P - J Neural Transm (Vienna) (2011)

Effect of joint administration of CGP 37849 and chlordiazepoxide (CDP) in the elevated plus-maze procedure in mice [the percentage of the time spent in the open arms (a), and the percentage of the open arms entries (b)]. CGP 37849 and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 8 mice per group) *p < 0.05 versus CGP 37849, ^p < 0.001 versus CDP, #p < 0.05 versus control (vehicle-treated group) (Bonferroni’s test)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104009&req=5

Fig1: Effect of joint administration of CGP 37849 and chlordiazepoxide (CDP) in the elevated plus-maze procedure in mice [the percentage of the time spent in the open arms (a), and the percentage of the open arms entries (b)]. CGP 37849 and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 8 mice per group) *p < 0.05 versus CGP 37849, ^p < 0.001 versus CDP, #p < 0.05 versus control (vehicle-treated group) (Bonferroni’s test)
Mentions: Chlordiazepoxide administered at a dose of 0.5 mg/kg or CGP 37849 administered at a dose of 0.312 mg/kg, both given alone, did not change the percentage of the time spent and also entries into the open arms with the exception of CDP, which significantly increased this latter measure (Fig. 1). The joint administration of CDP and CGP 37849 significantly increased the percentage of the time spent in the open arms (Fig. 1a) and enhanced the number of entries into open arms (Fig. 1b). A two-way ANOVA demonstrated lack of effect of CDP [F(1, 28) = 1.91, p = 0.1777], significant effect of CGP 37849 [F(1, 28) = 26.38, p < 0.0001] and significant interaction [F(1, 28) = 8.02, p = 0.0085] in the time spent in open arms, while a significant effect of CDP [F(1, 28) = 15.301, p = 0.0005], no effect of CGP 37849 [F(1, 28) = 2.93, p = 0.09882] and no interaction [F(1, 28) = 0.0, p = 0.9492] in the open arm entries.Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland. ewa.poleszak@umlub.pl

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus