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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 N-methyl-d-aspartate (NMDA) on the action of 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)]. NMDA and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 10 mice per group) *p < 0.001 versus CDP, #p < 0.001, versus control (vehicle-treated group) (Bonferroni’s test)
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Fig4: Effect of N-methyl-d-aspartate (NMDA) on the action of 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)]. NMDA and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 10 mice per group) *p < 0.001 versus CDP, #p < 0.001, versus control (vehicle-treated group) (Bonferroni’s test)

Mentions: Chlordiazepoxide given at a dose of 2 mg/kg produced anxiolytic-like effect significantly increasing the percentage of the time spent in the open arms and increasing the percentage of the entries into the open arms (Fig. 4). The increase in percentage of the time spent in the open arms induced by CDP (2 mg/kg) was significantly reversed by NMDA (75 mg/kg) (Fig. 4a). The increase in the number of the open arm entries induced by CDP (2 mg/kg) was significantly decreased by NMDA (Fig. 4b). NMDA given alone had no effect on either the time spent or the entries into the open arms (Fig. 4). A two-way ANOVA demonstrated a significant effect of CDP [F(1, 36) = 45.98, p < 0.0001], a significant effect of NMDA [F(1, 36) = 21.37, p < 0.0001] and a significant interaction [F(1, 36) = 21.19, p < 0.0001] in the time spent in open arms, and a similarly significant effect of CDP [F(1, 36 = 15.87, p = 0.0003], a significant effect of NMDA [F(1, 36) = 8.11, p = 0.0072] and a significant interaction [F(1, 36) = 11.91, p = 0.0014] in the open arm entries.Fig. 4


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 N-methyl-d-aspartate (NMDA) on the action of 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)]. NMDA and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 10 mice per group) *p < 0.001 versus CDP, #p < 0.001, versus control (vehicle-treated group) (Bonferroni’s test)
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Related In: Results  -  Collection

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

Fig4: Effect of N-methyl-d-aspartate (NMDA) on the action of 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)]. NMDA and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 10 mice per group) *p < 0.001 versus CDP, #p < 0.001, versus control (vehicle-treated group) (Bonferroni’s test)
Mentions: Chlordiazepoxide given at a dose of 2 mg/kg produced anxiolytic-like effect significantly increasing the percentage of the time spent in the open arms and increasing the percentage of the entries into the open arms (Fig. 4). The increase in percentage of the time spent in the open arms induced by CDP (2 mg/kg) was significantly reversed by NMDA (75 mg/kg) (Fig. 4a). The increase in the number of the open arm entries induced by CDP (2 mg/kg) was significantly decreased by NMDA (Fig. 4b). NMDA given alone had no effect on either the time spent or the entries into the open arms (Fig. 4). A two-way ANOVA demonstrated a significant effect of CDP [F(1, 36) = 45.98, p < 0.0001], a significant effect of NMDA [F(1, 36) = 21.37, p < 0.0001] and a significant interaction [F(1, 36) = 21.19, p < 0.0001] in the time spent in open arms, and a similarly significant effect of CDP [F(1, 36 = 15.87, p = 0.0003], a significant effect of NMDA [F(1, 36) = 8.11, p = 0.0072] and a significant interaction [F(1, 36) = 11.91, p = 0.0014] in the open arm entries.Fig. 4

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