Sites and mechanisms of dependence in the myenteric plexus of guinea pig ileum.

The isolated guinea pig ileum provides a model in which drug dependence can be induced in normal neurons. The characteristics of opiate dependence in the ileum closely resemble those of dependence in whole animals. Convergent dependence on normorphine, clonidine, and adenosine can be separately induced in the ileum in vitro. Use of selective antagonists indicates that both acetylcholine and substance P participate in the withdrawal response associated with all three of these dependencies. The demonstration that adenosine derivatives suppress opiate withdrawal in the guinea pig ileum and in mice raises the possibility that they might act similarly in man. The point at which the dependencies on normorphine, clonidine, and adenosine converge is probably below their separate recognition sites and is possibly at the level of adenylate cyclase regulation.