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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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Effect of joint administration of d-serine (DS) and a imipramine (IMI), b fluoxetine (FX) or c reboxetine (RB) on the total duration of immobility in the forced swim test in mice. DS was administered intracerebroventricularly (i.c.v.) 15 min before the test and antidepressant drugs were administered i.p. 45 min before DS. The values represent means ± SEM of 9–12 mice. *p < 0.05, ***p < 0.001 versus control (vehicle-treated animals); #p < 0.05, ##p < 0.01 versus respective antidepressant drug given alone (Student–Newman–Keuls post hoc test)
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Fig4: Effect of joint administration of d-serine (DS) and a imipramine (IMI), b fluoxetine (FX) or c reboxetine (RB) on the total duration of immobility in the forced swim test in mice. DS was administered intracerebroventricularly (i.c.v.) 15 min before the test and antidepressant drugs were administered i.p. 45 min before DS. The values represent means ± SEM of 9–12 mice. *p < 0.05, ***p < 0.001 versus control (vehicle-treated animals); #p < 0.05, ##p < 0.01 versus respective antidepressant drug given alone (Student–Newman–Keuls post hoc test)

Mentions: The effects of a combined administration of IMI and d-serine (the glycine B receptor agonist) on the total duration of immobility in mice are shown in Fig. 4a [ANOVA: F(3,33) = 12.74, p < 0.0001]. IMI at a dose of 30 mg/kg significantly reduced the immobility time in mice. d-serine alone, given i.c.v. at a dose of 100 nmol/mouse, had no effect on the immobility time. However, when combined with IMI, it abolished the IMI-induced antidepressant-like effect.Fig. 4


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)

Effect of joint administration of d-serine (DS) and a imipramine (IMI), b fluoxetine (FX) or c reboxetine (RB) on the total duration of immobility in the forced swim test in mice. DS was administered intracerebroventricularly (i.c.v.) 15 min before the test and antidepressant drugs were administered i.p. 45 min before DS. The values represent means ± SEM of 9–12 mice. *p < 0.05, ***p < 0.001 versus control (vehicle-treated animals); #p < 0.05, ##p < 0.01 versus respective antidepressant drug given alone (Student–Newman–Keuls post hoc test)
© Copyright Policy
Related In: Results  -  Collection

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

Fig4: Effect of joint administration of d-serine (DS) and a imipramine (IMI), b fluoxetine (FX) or c reboxetine (RB) on the total duration of immobility in the forced swim test in mice. DS was administered intracerebroventricularly (i.c.v.) 15 min before the test and antidepressant drugs were administered i.p. 45 min before DS. The values represent means ± SEM of 9–12 mice. *p < 0.05, ***p < 0.001 versus control (vehicle-treated animals); #p < 0.05, ##p < 0.01 versus respective antidepressant drug given alone (Student–Newman–Keuls post hoc test)
Mentions: The effects of a combined administration of IMI and d-serine (the glycine B receptor agonist) on the total duration of immobility in mice are shown in Fig. 4a [ANOVA: F(3,33) = 12.74, p < 0.0001]. IMI at a dose of 30 mg/kg significantly reduced the immobility time in mice. d-serine alone, given i.c.v. at a dose of 100 nmol/mouse, had no effect on the immobility time. However, when combined with IMI, it abolished the IMI-induced antidepressant-like effect.Fig. 4

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