Animal were considered to be immobile, whenever it remained floating passively in the water in a slightly hunched but upright position, its nose above the water surface. Tukey’s 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 Lyn-IN-1 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. 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 Lyn-IN-1 for the conduct of tests in the present study. Open in a separate window Figure 1 Temporal sequence of the tests conducted in the present study Procedure for Evaluation of Depression in Mice Forced swim test in micePorsolt’s FST was used as a model for evaluating depression in mice.[12] Drugs were administered 30 min prior to the start of experimentation. Animals were individually forced to swim inside a glass jar containing 10 cm of water maintained at 23C25C. After the initial 1C2 min of vigorous activity, the animals Rabbit Polyclonal to Sumo1 showed periods of immobility by floating with minimum movements. Animal were considered to be immobile, whenever it remained floating passively in the water in a slightly hunched but upright position, its nose above the water surface. The total immobility time for the period of 6 min will be recorded. The immobility time was recorded by an observer who was blind to the drug treatment. Tail suspension test in miceThe total duration of immobility time was also checked by the tail suspension test (TST) according to the method described as a means of evaluating potential antidepressants[13] with slight modifications. Treatment was administered 30 min before the test, and then the mice were suspended 50 cm above the floor by adhesive tape placed approximately 1 cm from the tip of the tail. A test was conducted in 6 min and immobility time was calculated.[14,15] Mice were considered immobile only if they hung passively and completely without any body movements. Step down avoidance paradigm in miceStep down behavior was employed to examine memory loss by the procedure as described by Vignisse test. All results are shown as mean standard error of the mean. ED50 was calculated using Graph Pad Prism 6 Software developed by GraphPad Software, Inc., USA. Results Effects of Various Treatments on Forced Swimming Test in MiceThe ED50 values of different antidepressants obtained from the FST were citalopram 12.5 mg/kg p.o., duloxetine 42.8 mg/kg p.o., fluvoxamine 17.5 mg/kg p.o., venlafaxine 15.7 mg/kg p.o. in mice [Table 1]. Table 1 ED50 of antidepressants calculated in forced swim test model of depression in mice Open in a separate window Treatment with pharmacological interventions rejected the null hypothesis in FST and there was a difference observed within the mean values of different treatments (SS-15916, DF-8, MS-1990, (8, 45)-13.87, 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%, Lyn-IN-1 and 95.5%, respectively, compared to the vehicle control in mice. Thus, citalopram in combination with scopolamine exhibited sub-addictive effect compared to scopolamine and citalopram and fluvoxamine 0.0001) synergistic hyper-additive antidepressive-like effect compared to scopolamine and venlafaxine treatment [Figure 2]. Open in a separate window Figure 2 Tail suspension test in mice. All values are represented as mean standard error of the mean; = 6, *represents significant difference ( 0.05) of the combination of venlafaxine and scopolamine compared with venlafaxine and scopolamine using analysis of variance Tukey’s test Effects of Various Treatments Lyn-IN-1 on Tail Suspension Test.