Experiments on whole animals, guinea pig isolated ileum, individual neurones in situ and
cultured neuroblastoma–glioma hybrid cells indicate that opiate dependence and
associated tolerance develop within neurones bearing specific opiate receptors (opiate-
sensitive neurones). The essential change appears to be an hypertrophy of the cyclic AMP
system, in response to inhibition by opiate of a neuronal adenylate cyclase.