On one database (mailfile) I have a slow response time when trying to acces it (not all the time, but often). This is the only database that I can observed this problem. This databse is used by some peoples (between 5 and 15).
We had a simlilar issue with a web application that moved from R6 to ND6. Turned out to be an unread mark issue. If all these apply to you, turning off maintaining the unread marks might be a good test.