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A complex interaction between glycine/NMDA receptors and serotonergic/noradrenergic antidepressants in the forced swim test in mice.

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

Bottom Line: L-701,324 and D: -cycloserine given with reboxetine (administered in subeffective doses) did not change the behavior of animals in the forced swim test.The depletion of serotonin by p-CPA did not alter baseline activity in the forced swim test.Moreover, the antidepressant-like effects of imipramine, fluoxetine and reboxetine were abolished by D: -serine, a full agonist of glycine/NMDA receptors.

View Article: PubMed Central - PubMed

Affiliation: Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, Lublin, Poland. ewa.poleszak@umlub.pl

ABSTRACT
Both clinical and preclinical studies demonstrate the antidepressant activity of the functional NMDA receptor antagonists. In this study, we assessed the effects of two glycine/NMDA receptor ligands, namely L-701,324 (antagonist) and D: -cycloserine (a partial agonist) on the action of antidepressant drugs with different pharmacological profiles in the forced swim test in mice. Swim sessions were conducted by placing mice individually in glass cylinders filled with warmed water for 6 min. The duration of behavioral immobility during the last 4 min of the test was evaluated. The locomotor activity of mice was measured with photoresistor actimeters. L-701,324 and D: -cycloserine given with reboxetine (administered in subeffective doses) did not change the behavior of animals in the forced swim test. A potentiating effect was seen when both tested glycine site ligands were given concomitantly with imipramine or fluoxetine in this test. The lesion of noradrenaline nerve terminals produced by DSP-4 neither altered the baseline activity nor influenced the antidepressant-like action of L-701,324 or D: -cycloserine. The depletion of serotonin by p-CPA did not alter baseline activity in the forced swim test. However, it completely antagonized the antidepressant-like action produced by L-701,324 and D: -cycloserine. Moreover, the antidepressant-like effects of imipramine, fluoxetine and reboxetine were abolished by D: -serine, a full agonist of glycine/NMDA receptors. The present study demonstrates that glycine/NMDA receptor functional antagonists enhance the antidepressant-like action of serotonin, but not noradrenaline-based antidepressants and such their activity seems to depend on serotonin rather than noradrenaline pathway.

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The effects of pre-treatment of animals with p-CPA and DSP-4 on the antidepressant-like effects of a–b L-701,324 and c–dd-cycloserine (DCS) in the forced swim test in mice. p-CPA (200 mg/kg, i.p.) was administered once daily for 3 consecutive days. DSP-4 was administered at a dose of 50 mg/kg 4 days prior to the test. The values represent means ± SEM of 9–10 mice. **p < 0.01, ***p < 0.001 versus control (vehicle-treated animals); ##p < 0.01, ###p < 0.001 versus, respective glycine/NMDA ligand given alone (Student–Newman–Keuls post hoc test)
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Fig2: The effects of pre-treatment of animals with p-CPA and DSP-4 on the antidepressant-like effects of a–b L-701,324 and c–dd-cycloserine (DCS) in the forced swim test in mice. p-CPA (200 mg/kg, i.p.) was administered once daily for 3 consecutive days. DSP-4 was administered at a dose of 50 mg/kg 4 days prior to the test. The values represent means ± SEM of 9–10 mice. **p < 0.01, ***p < 0.001 versus control (vehicle-treated animals); ##p < 0.01, ###p < 0.001 versus, respective glycine/NMDA ligand given alone (Student–Newman–Keuls post hoc test)

Mentions: The effects of L-701,324 and p-CPA on the behavior in the FST are shown in Fig. 2a [ANOVA: F(3,33) = 7.629, p = 0.0005]. In controls, L-701,324 (4 mg/kg) significantly reduced the immobility time in comparison with saline. The administration of p-CPA (200 mg/kg i.p. once a day for 3 consecutive days) did not alter baseline behavior during the FST. However, depletion of serotonin completely blocked the decrease of the immobility time elicited by L-701,324.Fig. 2


A complex interaction between glycine/NMDA receptors and serotonergic/noradrenergic antidepressants in the forced swim test in mice.

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

The effects of pre-treatment of animals with p-CPA and DSP-4 on the antidepressant-like effects of a–b L-701,324 and c–dd-cycloserine (DCS) in the forced swim test in mice. p-CPA (200 mg/kg, i.p.) was administered once daily for 3 consecutive days. DSP-4 was administered at a dose of 50 mg/kg 4 days prior to the test. The values represent means ± SEM of 9–10 mice. **p < 0.01, ***p < 0.001 versus control (vehicle-treated animals); ##p < 0.01, ###p < 0.001 versus, respective glycine/NMDA ligand given alone (Student–Newman–Keuls post hoc test)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3197923&req=5

Fig2: The effects of pre-treatment of animals with p-CPA and DSP-4 on the antidepressant-like effects of a–b L-701,324 and c–dd-cycloserine (DCS) in the forced swim test in mice. p-CPA (200 mg/kg, i.p.) was administered once daily for 3 consecutive days. DSP-4 was administered at a dose of 50 mg/kg 4 days prior to the test. The values represent means ± SEM of 9–10 mice. **p < 0.01, ***p < 0.001 versus control (vehicle-treated animals); ##p < 0.01, ###p < 0.001 versus, respective glycine/NMDA ligand given alone (Student–Newman–Keuls post hoc test)
Mentions: The effects of L-701,324 and p-CPA on the behavior in the FST are shown in Fig. 2a [ANOVA: F(3,33) = 7.629, p = 0.0005]. In controls, L-701,324 (4 mg/kg) significantly reduced the immobility time in comparison with saline. The administration of p-CPA (200 mg/kg i.p. once a day for 3 consecutive days) did not alter baseline behavior during the FST. However, depletion of serotonin completely blocked the decrease of the immobility time elicited by L-701,324.Fig. 2

Bottom Line: L-701,324 and D: -cycloserine given with reboxetine (administered in subeffective doses) did not change the behavior of animals in the forced swim test.The depletion of serotonin by p-CPA did not alter baseline activity in the forced swim test.Moreover, the antidepressant-like effects of imipramine, fluoxetine and reboxetine were abolished by D: -serine, a full agonist of glycine/NMDA receptors.

View Article: PubMed Central - PubMed

Affiliation: Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, Lublin, Poland. ewa.poleszak@umlub.pl

ABSTRACT
Both clinical and preclinical studies demonstrate the antidepressant activity of the functional NMDA receptor antagonists. In this study, we assessed the effects of two glycine/NMDA receptor ligands, namely L-701,324 (antagonist) and D: -cycloserine (a partial agonist) on the action of antidepressant drugs with different pharmacological profiles in the forced swim test in mice. Swim sessions were conducted by placing mice individually in glass cylinders filled with warmed water for 6 min. The duration of behavioral immobility during the last 4 min of the test was evaluated. The locomotor activity of mice was measured with photoresistor actimeters. L-701,324 and D: -cycloserine given with reboxetine (administered in subeffective doses) did not change the behavior of animals in the forced swim test. A potentiating effect was seen when both tested glycine site ligands were given concomitantly with imipramine or fluoxetine in this test. The lesion of noradrenaline nerve terminals produced by DSP-4 neither altered the baseline activity nor influenced the antidepressant-like action of L-701,324 or D: -cycloserine. The depletion of serotonin by p-CPA did not alter baseline activity in the forced swim test. However, it completely antagonized the antidepressant-like action produced by L-701,324 and D: -cycloserine. Moreover, the antidepressant-like effects of imipramine, fluoxetine and reboxetine were abolished by D: -serine, a full agonist of glycine/NMDA receptors. The present study demonstrates that glycine/NMDA receptor functional antagonists enhance the antidepressant-like action of serotonin, but not noradrenaline-based antidepressants and such their activity seems to depend on serotonin rather than noradrenaline pathway.

Show MeSH
Related in: MedlinePlus