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Modulation of muscarinic system with serotonin-norepinephrine reuptake inhibitor antidepressant attenuates depression in mice.

Singh P, Singh TG - Indian J Pharmacol (2015 Jul-Aug)

Bottom Line: Behavioral studies indicated that only antidepressant venlafaxine with scopolamine resulted in 95.5% and 93.6% reduction in immobility time compared to the vehicle control in FST and TST, respectively.This is significant (P < 0.0001) synergistic hyper-additive antidepressive-like effect compared to scopolamine per se and venlafaxine per se treatment effects in antidepressant paradigms.The present results suggest the concoction of scopolamine with venlafaxine for enhanced synergistic antidepressive effects with the reduction of dose.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Patiala, Punjab, India.

ABSTRACT

Objective: Several studies suggest that muscarinic receptor antagonist scopolamine is a rapidly acting antidepressant for the treatment-resistant depression. Therefore, this study was carried out to investigate the possibility of synergistic potential of scopolamine with antidepressants for the treatment of depression without memory impairment in mice.

Materials and methods: Antidepressants such as citalopram, duloxetine, fluvoxamine, and venlafaxine at their median effective dose that is 12.5, 42.8, 17.5, 15.7 mg/kg p.o., respectively, were evaluated in combination with scopolamine 0.2 mg/kg intraperitoneally for the synergistic potential for ameliorating depression in Swiss albino mice. A battery of tests including forced swim test (FST) and tail suspension test (TST) were performed in all the groups comprising vehicle control, scopolamine, antidepressants per se, and the combinations of antidepressants with scopolamine. This was followed by the locomotor activity and memory tests.

Results: Behavioral studies indicated that only antidepressant venlafaxine with scopolamine resulted in 95.5% and 93.6% reduction in immobility time compared to the vehicle control in FST and TST, respectively. This is significant (P < 0.0001) synergistic hyper-additive antidepressive-like effect compared to scopolamine per se and venlafaxine per se treatment effects in antidepressant paradigms. All the data were evaluated using the one-way analysis of variance followed by individual comparisons using Tukey's post-hoc test. Control open field studies demonstrated no significant increase in general locomotion after co-administration of the compounds. Step down avoidance paradigm confirmed that scopolamine at the selected dose has no cognition deficit in any mice.

Conclusions: The dose of scopolamine selected for synergistic potential has no detrimental effect on memory. The present results suggest the concoction of scopolamine with venlafaxine for enhanced synergistic antidepressive effects with the reduction of dose.

No MeSH data available.


Related in: MedlinePlus

Step down memory test in mice. None of the pharmacological intervention modulated number of mistakes significantly compared to vehicle control in mice. All values are represented as mean ± standard error of the mean; n = 6 and calculated using analysis of variance Tukey's post-hoc test
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Figure 5: Step down memory test in mice. None of the pharmacological intervention modulated number of mistakes significantly compared to vehicle control in mice. All values are represented as mean ± standard error of the mean; n = 6 and calculated using analysis of variance Tukey's post-hoc test

Mentions: In step down test, the vehicle control group showed the SDL 86.5 ± 9.7 s and none of the treatment either alone or in combination were found to significantly (P < 0.05) alter it. Similarly, no significant effect was observed in case of a number of mistakes made by treatment groups when compared to the vehicle control [Figure 5]. Thus, concludes that none of the treatments have any detrimental effect on memory.


Modulation of muscarinic system with serotonin-norepinephrine reuptake inhibitor antidepressant attenuates depression in mice.

Singh P, Singh TG - Indian J Pharmacol (2015 Jul-Aug)

Step down memory test in mice. None of the pharmacological intervention modulated number of mistakes significantly compared to vehicle control in mice. All values are represented as mean ± standard error of the mean; n = 6 and calculated using analysis of variance Tukey's post-hoc test
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4527059&req=5

Figure 5: Step down memory test in mice. None of the pharmacological intervention modulated number of mistakes significantly compared to vehicle control in mice. All values are represented as mean ± standard error of the mean; n = 6 and calculated using analysis of variance Tukey's post-hoc test
Mentions: In step down test, the vehicle control group showed the SDL 86.5 ± 9.7 s and none of the treatment either alone or in combination were found to significantly (P < 0.05) alter it. Similarly, no significant effect was observed in case of a number of mistakes made by treatment groups when compared to the vehicle control [Figure 5]. Thus, concludes that none of the treatments have any detrimental effect on memory.

Bottom Line: Behavioral studies indicated that only antidepressant venlafaxine with scopolamine resulted in 95.5% and 93.6% reduction in immobility time compared to the vehicle control in FST and TST, respectively.This is significant (P < 0.0001) synergistic hyper-additive antidepressive-like effect compared to scopolamine per se and venlafaxine per se treatment effects in antidepressant paradigms.The present results suggest the concoction of scopolamine with venlafaxine for enhanced synergistic antidepressive effects with the reduction of dose.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Patiala, Punjab, India.

ABSTRACT

Objective: Several studies suggest that muscarinic receptor antagonist scopolamine is a rapidly acting antidepressant for the treatment-resistant depression. Therefore, this study was carried out to investigate the possibility of synergistic potential of scopolamine with antidepressants for the treatment of depression without memory impairment in mice.

Materials and methods: Antidepressants such as citalopram, duloxetine, fluvoxamine, and venlafaxine at their median effective dose that is 12.5, 42.8, 17.5, 15.7 mg/kg p.o., respectively, were evaluated in combination with scopolamine 0.2 mg/kg intraperitoneally for the synergistic potential for ameliorating depression in Swiss albino mice. A battery of tests including forced swim test (FST) and tail suspension test (TST) were performed in all the groups comprising vehicle control, scopolamine, antidepressants per se, and the combinations of antidepressants with scopolamine. This was followed by the locomotor activity and memory tests.

Results: Behavioral studies indicated that only antidepressant venlafaxine with scopolamine resulted in 95.5% and 93.6% reduction in immobility time compared to the vehicle control in FST and TST, respectively. This is significant (P < 0.0001) synergistic hyper-additive antidepressive-like effect compared to scopolamine per se and venlafaxine per se treatment effects in antidepressant paradigms. All the data were evaluated using the one-way analysis of variance followed by individual comparisons using Tukey's post-hoc test. Control open field studies demonstrated no significant increase in general locomotion after co-administration of the compounds. Step down avoidance paradigm confirmed that scopolamine at the selected dose has no cognition deficit in any mice.

Conclusions: The dose of scopolamine selected for synergistic potential has no detrimental effect on memory. The present results suggest the concoction of scopolamine with venlafaxine for enhanced synergistic antidepressive effects with the reduction of dose.

No MeSH data available.


Related in: MedlinePlus