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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 d-cycloserine (DCS) 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)]. L-701,324 and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 9–10 mice per group) *p < 0.001 versus DCS, ^p < 0.05, ^^p < 0.001 versus CDP (Bonferroni’s test)
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Fig3: Effect of joint administration of d-cycloserine (DCS) 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)]. L-701,324 and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 9–10 mice per group) *p < 0.001 versus DCS, ^p < 0.05, ^^p < 0.001 versus CDP (Bonferroni’s test)

Mentions: Chlordiazepoxide administered at a dose of 0.5 mg/kg did not change either the percentage of the time spent (Fig. 3a) or the number of entries into open arms (Fig. 3b). d-Cycloserine administered singly at a dose of 2.5 mg/kg remained also without any effect on both of these measures (Fig. 3a, b). CDP administered at an ineffective per se dose of 0.5 mg/kg and d-cycloserine administered at such a dose of 2.5 mg/kg significantly increased the percentage of the time spent in the open arms (Fig. 3a) and enhanced the number of entries into open arms (Fig. 3b). A two-way ANOVA demonstrated a significant effect of CDP [F(1, 34) = 24.83, p < 0.0001], a significant effect of DCS [F(1, 34) = 8.73, p = 0.0057] and a significant interaction [F(1, 34) = 13.35, p = 0.0009] in the time spent in the open arms, while a significant effect of CDP [F(1, 34) = 19.50, p < 0.0001], a significant effect of DCS [F(1, 34) = 4.31, p = 0.0451] and no interaction [F(1, 34) = 2.93, p = 0.0956] in the open arm entries.Fig. 3


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 d-cycloserine (DCS) 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)]. L-701,324 and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 9–10 mice per group) *p < 0.001 versus DCS, ^p < 0.05, ^^p < 0.001 versus CDP (Bonferroni’s test)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3104009&req=5

Fig3: Effect of joint administration of d-cycloserine (DCS) 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)]. L-701,324 and CDP was administered i.p. 60 min before the test. The values represent the mean ± SEM (n = 9–10 mice per group) *p < 0.001 versus DCS, ^p < 0.05, ^^p < 0.001 versus CDP (Bonferroni’s test)
Mentions: Chlordiazepoxide administered at a dose of 0.5 mg/kg did not change either the percentage of the time spent (Fig. 3a) or the number of entries into open arms (Fig. 3b). d-Cycloserine administered singly at a dose of 2.5 mg/kg remained also without any effect on both of these measures (Fig. 3a, b). CDP administered at an ineffective per se dose of 0.5 mg/kg and d-cycloserine administered at such a dose of 2.5 mg/kg significantly increased the percentage of the time spent in the open arms (Fig. 3a) and enhanced the number of entries into open arms (Fig. 3b). A two-way ANOVA demonstrated a significant effect of CDP [F(1, 34) = 24.83, p < 0.0001], a significant effect of DCS [F(1, 34) = 8.73, p = 0.0057] and a significant interaction [F(1, 34) = 13.35, p = 0.0009] in the time spent in the open arms, while a significant effect of CDP [F(1, 34) = 19.50, p < 0.0001], a significant effect of DCS [F(1, 34) = 4.31, p = 0.0451] and no interaction [F(1, 34) = 2.93, p = 0.0956] in the open arm entries.Fig. 3

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