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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

Temporal sequence of the tests conducted in the present study
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Figure 1: Temporal sequence of the tests conducted in the present study

Mentions: Scopolamine, citalopram, duloxetine, fluvoxamine, and venlafaxine purchased from Sigma-Aldrich were used in the present study. ED50 doses of different antidepressants were first calculated in forced swim test (FST) using dose response curve with doses in geometrical progression versus immobility time in seconds. ED50 doses were then used in combination with scopolamine to study for synergistic potential. The dose of scopolamine 0.2 mg/kg i.p. was selected based on previous research work done on scopolamine.[10] According to Ji and Zhang,[11] scopolamine at this dose, significantly decreased the immobility time (P < 0.001) in FST, but had no influence on the locomotor activity in open field test at this dose. Animals were randomized on the basis of their body weight into different groups such as vehicle p.o. (Group 1), scopolamine i.p. 0.2 mg/kg (Group 2), citalopram p.o. 12.5 mg/kg (Group 3), citalopram p.o. 12.5 mg/kg + scopolamine i.p. 0.2 mg/kg (Group 4), duloxetine p.o. 42.8 mg/kg (Group 5), duloxetine p.o. 42.8 mg/kg + scopolamine i.p. 0.2 mg/kg (Group 6), fluvoxamine p.o. 17.5 mg/kg (Group 7), fluvoxamine p.o. 17.5 mg/kg + scopolamine i.p. 0.2 mg/kg (Group 8), venlafaxine p.o. 15.7 mg/kg (Group 9), venlafaxine p.o. 15.7 mg/kg + scopolamine i.p. 0.2 mg/kg (Group 10). Figure 1 explains the general temporal sequence for the conduct of tests in the present study.


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

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

Temporal sequence of the tests conducted in the present study
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Temporal sequence of the tests conducted in the present study
Mentions: Scopolamine, citalopram, duloxetine, fluvoxamine, and venlafaxine purchased from Sigma-Aldrich were used in the present study. ED50 doses of different antidepressants were first calculated in forced swim test (FST) using dose response curve with doses in geometrical progression versus immobility time in seconds. ED50 doses were then used in combination with scopolamine to study for synergistic potential. The dose of scopolamine 0.2 mg/kg i.p. was selected based on previous research work done on scopolamine.[10] According to Ji and Zhang,[11] scopolamine at this dose, significantly decreased the immobility time (P < 0.001) in FST, but had no influence on the locomotor activity in open field test at this dose. Animals were randomized on the basis of their body weight into different groups such as vehicle p.o. (Group 1), scopolamine i.p. 0.2 mg/kg (Group 2), citalopram p.o. 12.5 mg/kg (Group 3), citalopram p.o. 12.5 mg/kg + scopolamine i.p. 0.2 mg/kg (Group 4), duloxetine p.o. 42.8 mg/kg (Group 5), duloxetine p.o. 42.8 mg/kg + scopolamine i.p. 0.2 mg/kg (Group 6), fluvoxamine p.o. 17.5 mg/kg (Group 7), fluvoxamine p.o. 17.5 mg/kg + scopolamine i.p. 0.2 mg/kg (Group 8), venlafaxine p.o. 15.7 mg/kg (Group 9), venlafaxine p.o. 15.7 mg/kg + scopolamine i.p. 0.2 mg/kg (Group 10). Figure 1 explains the general temporal sequence for the conduct of tests in the present study.

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