PMC

Effect of serotonin and ritanserin on cell viability is cell line dependent. a: Effects of serotonin and ritanserin on cell viability in CnOb. Cell viability was assessed through a MTS assay of CnOb treated with escalating doses of serotonin or ritanserin. Decreased cell viability relative to the vehicle control is only observed at 50 μM serotonin (p = 0.013) and 50 μM ritanserin (p < 0.01). A greater decrease in viability is observed at 50 μM ritanserin than 50 μM serotonin (p < 0.01). Plotted values are mean cell viability +/− 95% confidence interval of mean. b: Effects of serotonin and ritanserin on cell viability in COS. Cell viability was assessed through a MTS assay of COS treated with escalating doses of serotonin, ritanserin, and ritanserin with concurrent serotonin (12.5 μM). Relative to the vehicle control, increased viability was observed at 3.125, 6.25, and 12.5 μM serotonin (p < 0.01). Conversely, a mild decrease in viability was observed at 6.25 μM ritanserin (p < 0.01) with marked decreased evident at 12.5, 25.0, and 50 μM (p < 0.01). Viability was greater at 6.25 and 12.5 μM ritanserin when concurrently incubated with serotonin (12.5 μM) than the viability observed with 6.25 and 12.5 μM ritanserin alone (p < 0.01). The calculated IC50 of ritanserin for COS is 6.3 μM. Plotted values are mean cell viability +/− 95% confidence interval of mean.

Effect of ritanserin on performance in AAPA task. (A) There is no change in total distance traveled during the session compared with control group or MK-801 group. However, a difference was found between 2.5 mg/kg ritanserin and 2.5 mg/kg ritanserin plus MK-801 (#, P < 0.05). (B) Concerning number of errors, MK-801 treatment impaired performance (***, P < 0.001) compared with the control group. However, both doses of ritanserin attenuated the effect of MK-801 (§§§, P < 0.001; §, P < 0.05, respectively) compared with the MK-801 group. Moreover, there is a difference between 2.5 mg/kg ritanserin and 2.5 mg/kg ritanserin plus MK-801 (#, P < 0.05). (C) Administration of MK-801 decreased the maximum time of avoidance (**, P < 0.01). Both doses of ritanserin blocked the worsening effect of MK-801 (§, P < 0.05).

Difference in number of trajectories was calculated by subtraction of ritanserin results from baseline vehicle measurements. In both groups the number of trajectories significantly decreases between wake and light SWS (LSWS) and vice versa after ritanserin (Rit) administration. Ritanserin significantly increased the number of trajectories of LSWS to deep SWS (DSWS) in UAO group. *p<0.05 comparing ritanserin results to baseline vehicle measurements in the same animals. #p<0.05 comparing change in trajectories between control and UAO groups.

Ritanserin induce caspase activity in COS. a: Effects of serotonin, and ritanserin on caspase activity in COS. Caspase activity increased with escalating concentrations of ritanserin, with mildly increased activity appreciated at 3.125 (p = 0.0170) and 12.5 μM (p = 0.025) and markedly increased activity present with 25.0 and 50.0 μM (p < 0.01). No difference in caspase activity between the DMSO vehicle control and any concentration of serotonin were observed. Concurrent incubation of ritanserin with 12.5 μM serotonin showed attenuated caspase activity at 3.125 (p = 0.049) and 6.25 μM ( p = 0.043) ritanserin relative to cells treated with ritanserin alone. Caspase activity in taurolidine treated cells, the positive control, was significantly greater than the vehicle control (p < 0.01). Plotted values are mean caspase activity +/− 95% confidence interval of mean. b: Caspase activity in COS treated with ritanserin in the presence or absence of a caspase inhibitor. Pre-incubation with the general capase inhibitor Z-VAD-FMK dramatically decreased caspase activity in COS cells treated with 12.5 μM ritanserin (p < 0.01). Plotted values are mean caspase activity +/− 95% confidence interval of mean.