Problems of drug dependence, 1979. Proceedings of the 41st Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc.

The basic principle is proposed that the neurone possessing specific opiate receptors (opiate-sensitive neurone) is the primary and suf- ficient site of opiate dependence and associated tolerance (ODT). The lines of experimental evidence that support this principle are: (a) in the dependent rat, drugs, such as atropine, that block trans- mission between neurones lessen some signs of withdrawal, intensify others and leave yet others unchanged, whereas opiates suppress and specific opiate antagonists intensify all withdrawal signs; (b) in the mouse and in the post-ganglionic myenteric plexus of the guinea- pig ileum, as dependence intensifies, so the effective concentration of naloxone falls below that at which naloxone interacts only with the opiate receptor; (c) ODT can be demonstrated in single neu- rones in situ in the rat cerebral cortex and the myenteric plexus of them-pig ileum; (d) ODT can be induced in the guinea- pig isolated ileum by exposure to opiate in conditions of trans- mitter blockade, both of ganglia and of the neuromuscular junction; (e) ODT develops in cultured opiate-sensitive neuroblastoma x glioma cells, which are functionally separate. The principle that the opiate-sensitive neurone is the primary and sufficient sit of ODT eliminates about half of the hypotheses that have been advanced to explain the mechanism of ODT and points towards a small group of hypotheses that postulate intracellular mechanisms.