Opiate tolerance and dependence induced in vitro in single myenteric neurones.

Abstract

OPIATES inhibit the firing of neurones in the myenteric plexus of the guinea pig ileum in a manner which is strikingly similar to their effects on many central neurones. This action on single neurone firing has been studied in detail1–3; it occurs at low concentrations of opiates1–3 and opioid peptides4, it is mimicked by the (−)- but not by the (+)-isomer of optical enantiomers, and it is reversed or prevented by the specific antagonist naloxone1–4. Naloxone has no effect on the firing rate of myenteric neurones removed from normal animals; however, it does cause a marked increase in the rate of firing of myenteric neurones taken from guinea pigs which have previously been made physically dependent on morphine5. Previous studies have shown that some signs of opiate tolerance and dependence can be induced in the guinea pig ileum both in vitro6,7 and in vivo8,9. In the present experiments, we have induced tolerance to the effects of opiates by exposing myenteric neurones to agonists in vitro for periods of about 24 h. Such neurones also showed manifestations of dependence on the presence of the opiate, in that their rate of firing increased markedly when the agonist was removed or when an antagonist was introduced. The tolerance and dependence were induced only by exposure to the (−)-isomer of enantiomeric agonists, and the increase in firing was precipitated only by the (−)-isomer of enantiomeric antagonists.