Morphine tolerance and dependence in noradrenaline neurones of the rat cerebral cortex

Summary By subcutaneous implantation of 2 or 13 morphine pellets (75 mg morphine/pellet), rats were made tolerant to, and dependent on narcotic analgesics. Occipital cortex slices from dependent animals and placebo-implanted controls were incubated with (-)-³H-noradrenaline and subsequently superfused with physiological salt solution. The accumulation of ³H-noradrenaline was not changed by pretreatment with 2, but was slightly decreased by pretreatment with 13 morphine pellets. The overflow of tritium evoked by electrical field stimulation was higher in slices from morphine-implanted rats than in those from placebo controls. Morphine and levorphanol, added in vitro, inhibited the stimulation-induced overflow of tritium at, similar concentrations and to a similar degree in slices from morphine-and placebo-pretreated animals. —It is concluded that, during chronic treatment with morphine, an adaptation takes place in the brain to compensate for the acute effect of narcotic analgesics, i.e. inhibition of the release of noradrenaline by nerve impulses. The chain of events from the drug-receptor interaction to the depression of the release process can be excluded as substrate of this adaptation. During with-drawal, the compensatory changes provoke an enhanced increase of extracellular noradrenaline during nerve impulses.