Problems of Drug Dependence, 1979: Proceedings of the 41st Annual Scientific Meeting.

Abstract

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.