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Many thanks for addressing all the issues.
[# PeerJ Staff Note - this decision was reviewed and approved by Bob Patton, a PeerJ Section Editor covering this Section #]
Dear Authors,
I have now received the reviewers' comments on your manuscript. The reviewers have recommended publication, but also suggest some minor revisions to your manuscript. Therefore, I invite you to respond to the reviewers' comments and revise your manuscript.
Sincerely,
The authors have successfully addressed my comments.
The authors have successfully addressed my comments.
The authors have successfully addressed my comments.
no comment
1. The author added a schematic diagram of the experimental design. I wonder why you didn’t have the groups treated with vehicle in your design? Please explain.
2. Please added your explain for estrous cycle and behavior test in the manuscript.
1. The authors have modified Figure 6 and 7, but please check Figure 1, and modify it as Figure 6 and 7 (with individual dots). Text size in Figure 3 and 4 is still too small to read.
2. The sample size is confusing. As you mentioned, with the death of three rats, it should be six. Why there are nine dots in figure 6 and 7? And in behavior test, it’s also nine in raw data.
1. Information about Table 3 “The distribution volume (Vz/F) and clearance (CLz/F)” showed in legend of Figure 5. It’s confusing.
2. Please reorganize the figures and tables, especially figure 3, 4 and 5. In my opinion, four or five figures totally is enough for this manuscript.
3. English language could be improved more.
The reviewers have recommended publication, but also suggest some major revisions to your manuscript. Therefore, I invite you to respond to the reviewers' comments and revise your manuscript.
Once again, thank you for submitting your manuscript to PeerJ and I look forward to receiving your revision as soon as possible.
[# PeerJ Staff Note: Please ensure that all review and editorial comments are addressed in a response letter and any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate. #]
This is an interesting study which showed that CUMS-induced depression altered the drug metabolic process of clopidogrel, and the change of CYP450 expression in depressive rats might contribute to the disturbance of clopidogrel pharmacokinetics.
However, the authors did not investigate the underlying mechanisms of why liver cytochrome metabolic enzymes could lead to a significant change in the efficacy of clopidogrel.
With the death of three rats, the sample size of 6 in the CUMS group may be too small to acquire reliable statistical results.
There are many grammar mistakes and typos. Please check through the manuscript. E.g., “modle” (should be “model”), “adlibitum” (“ad libitum”), “mightbe” (“might be”), etc. And there should be one space before brackets.
The authors did not investigate the underlying mechanisms of why liver cytochrome metabolic enzymes could lead to a significant change in the efficacy of clopidogrel.
With the death of three rats, the sample size of 6 in the CUMS group may be too small to acquire reliable statistical results.
No comment.
1. The experiment design is not clear. How many groups you have? When and how often you treated the rats with clopidogrel? The order of behavior tests? Please draw a schematic diagram of the experimental design.
It looks like there should be four groups totally but not two.
2. Have you take the effect of estrous cycle of on the results of behavior test into consideration？
3. Patient with ASC undergoing PCI need to take it for 6-12 months. So why you treat rats with clopidogrel only one time?
1. Please show all nine individual dots in every bar graph. And most of time we would like to show control data first and then the experimental group.
2. It’s hard to read the axis label of figure 2 & 3. And please keep the font and size of text of each figure consistents.
3. Why you didn’t choose tail suspension test or force swimming test? Open field test is not a typical behavioral test for stress induced depression. Is freezing time in OFT meaningful for stress-induced depression?
1. There is no space between a lot of text and parentheses in the text. The font and format of “P” are not uniform. Please check the whole manuscript carefully.
2. In result part, the data of behavioral test should be represent more clearly, like sucrose preference (Control 81.71… vs. CUMS 68.16…., p<….)
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