I think it's safe to say that before Twilight and Spike there wasn't much positive interaction between dragons and ponies. Or at the very least the negative interactions greatly outweighed them. I'd imagine that in the past Celestia and Luna were powerful enough to drive back any dragon aggression once made aware of it. Meanwhile the average dragon is powerful enough to cause quite a bit of harm to the average stray pony. So they likely stayed separate to avoid outright conflict.

Most of the other species with the possible exception of hippogriffs also seemed to have varying degrees of hostility to ponies. It looks like most of that is possibly cultural. If I had to guess way back in time when earth ponies, pegasi,and unicorns formed a single nation and along with the emergence of alicorns, ponies quickly grew to become a world superpower that the other groups viewed as infringing on their own way of life and possibly threatening.

Maintaining some level of trade and diplomacy would have been important but mostly everyone just keeps to their own corners so as not to provoke international incidents. The ponies may not know much about the other cultures but they are at least aware of and in contact with them.