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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

Tail suspension test in mice. All values are represented as mean ± standard error of the mean; n = 6, *represents significant difference (P < 0.05) of the combination of venlafaxine and scopolamine compared with venlafaxine per se and scopolamine per se using analysis of variance Tukey's post-hoc test
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Figure 2: Tail suspension test in mice. All values are represented as mean ± standard error of the mean; n = 6, *represents significant difference (P < 0.05) of the combination of venlafaxine and scopolamine compared with venlafaxine per se and scopolamine per se using analysis of variance Tukey's post-hoc test

Mentions: Treatment with pharmacological interventions rejected the hypothesis in FST and there was a difference observed within the mean values of different treatments (SS-15916, DF-8, MS-1990, F (8, 45)-13.87, P < 0.0001). Scopolamine, citalopram, duloxetine, fluvoxamine, venlafaxine, citalopram with scopolamine, duloxetine with scopolamine, fluvoxamine with scopolamine, and venlafaxine with scopolamine decreased the immobility time 37%, 45.3%, 56.5%, 42.8%, 36.3%, 61.1%, 55.8%, 62.5%, and 95.5%, respectively, compared to the vehicle control in mice. Thus, citalopram in combination with scopolamine exhibited sub-addictive effect compared to scopolamine per se and citalopram per se. similarly, fluvoxamine in combination with scopolamine exhibited sub-addictive effect compared to scopolamine per se and fluvoxamine per se; however, venlafaxine with scopolamine resulted in significant (P < 0.0001) synergistic hyper-additive antidepressive-like effect compared to scopolamine per se and venlafaxine per se treatment [Figure 2].


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

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

Tail suspension test in mice. All values are represented as mean ± standard error of the mean; n = 6, *represents significant difference (P < 0.05) of the combination of venlafaxine and scopolamine compared with venlafaxine per se and scopolamine per se 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 2: Tail suspension test in mice. All values are represented as mean ± standard error of the mean; n = 6, *represents significant difference (P < 0.05) of the combination of venlafaxine and scopolamine compared with venlafaxine per se and scopolamine per se using analysis of variance Tukey's post-hoc test
Mentions: Treatment with pharmacological interventions rejected the hypothesis in FST and there was a difference observed within the mean values of different treatments (SS-15916, DF-8, MS-1990, F (8, 45)-13.87, P < 0.0001). Scopolamine, citalopram, duloxetine, fluvoxamine, venlafaxine, citalopram with scopolamine, duloxetine with scopolamine, fluvoxamine with scopolamine, and venlafaxine with scopolamine decreased the immobility time 37%, 45.3%, 56.5%, 42.8%, 36.3%, 61.1%, 55.8%, 62.5%, and 95.5%, respectively, compared to the vehicle control in mice. Thus, citalopram in combination with scopolamine exhibited sub-addictive effect compared to scopolamine per se and citalopram per se. similarly, fluvoxamine in combination with scopolamine exhibited sub-addictive effect compared to scopolamine per se and fluvoxamine per se; however, venlafaxine with scopolamine resulted in significant (P < 0.0001) synergistic hyper-additive antidepressive-like effect compared to scopolamine per se and venlafaxine per se treatment [Figure 2].

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