Can percocet interfere with serotonin in the brain and bring on full blown depression in a person with depression history.?

Yes: Yes, opiate medication use, which is one of the ingredients in Percocet can cause depression, and someone with a past history of depression would be at higher risk for this side effect. Further, sometimes antidepressant medication doesn't work as well to treat a depression brought on by opiate med use until the person reduces or stops using the opiate medication.