Inhibition of neuroeffector transmission by morphine in the vas deferens of naive and morphine-treated mice.

1 The amplitude of excitatory junction potentials (e.j.ps) recorded intracellularly from smooth muscle cells of the mouse vas deferens varied with the strength of stimulation. Normorphine (0.4, 2 and 10 microM) shifted the stimulus-response curve to the right, without any change in slope. This shift of the curve was proportional to the concentration of the opiate in the bath. Naloxone (0.4 and 2 microM) antagonized this effect of normorphine. 2 The action of normorphine (2 and 10 microM) was studied in vasa deferentia prepared from control mice and mice that had been implanted with morphine pellets. Both groups of tissues were continuously exposed to a low concentration of normorphine (0.4 microM), to simulate the plasma concentration in the morphine-treated mice. Addition of 10 microM normorphine produced a parallel displacement of the curve in vasa deferentia from control animals, and a non-parallel displacement in tissues from morphine pellet-implanted mice. In the preparations from morphine-treated mice a pronounced degree of tolerance to normorphine was observed at a low stimulus strength. 3 Naloxone (0.4 and 2 microM) had a greater effect on vasa deferentia prepared from morphine-treated animals than on tissues from control mice, when both organs were continuously exposed to 0.4 microM normorphine. The difference in the effect of the antagonist in the two groups of preparations was absent when the incubating solution contained 2 microM normorphine. 4 It is concluded that a low intensity of stimulation the e.j.ps are more readily depressed by normorphine and also the degree of tolerance displayed is larger than at a high intensity of stimulation.