Influence of morphine and naloxone on the release of noradrenaline from rat brain cortex slices

Summary

In slices of rat brain cortex preincubated with (−)-³H-noradrenaline, the influence of morphine and naloxone on the efflux of tritium was investigated. The spontaneous outflow of tritium was not changed by 10⁻⁷–10⁻⁵ M morphine and by 10⁻⁶–10⁻⁴ M naloxone, but was accelerated by 10⁻⁴ M morphine. Electrical field stimulation augmented tritium outflow. The overflow evoked per ppulse decreased as the frequency of stimulation was increased from 0.3 to 3 Hz, but remained approximately constant when it was further increased to 10 Hz. At frequencies of 0.3, 1, and 3 Hz, but not at 10 Hz, morphine in concentrations of 10⁻⁷–10⁻⁵ M depressed the stimulation-induced overflow of tritium. 10⁻⁴ M morphine did not influence the overflow induced by stimulation at 0.3 and 1 Hz and increased that evoked by stimulation at 10 Hz. Naloxone (10⁻⁶–10⁻⁴ M) did not change the response to stimulation. In the presence of 10⁻⁴ M naloxone, 10⁻⁶ M morphine did not diminish, and 10⁻⁵ M morphine even enhanced the stimulation-induced overflow of tritium. The inhibitory effect of 10⁻⁶ M morphine was not reduced, after tyrosine hydroxylase had been blocked by α-methyltyrosine-methylester. It is concluded that morphine through an action on specific opiate receptors inhibits the release of transmitter from cerebrocortical noradrenergic neurones evoked by nerve impulses. By an action unrelated to opiate receptors, morphine at high concentrations increases the stimulation-induced overflow of noradrenaline, presumably by inhibiting its re-uptake into nerve endings.