The dependence of excitatory junction potential amplitude on the external calcium concentration in narcotic tolerant mouse vas deferens

Abstract

The dependence of neurotransmitter secretion on external calcium ions during development of opiate tolerance in the mouse vas deferens was studied. The writhing response of mice to an i.p. injection of acetylcholine was inhibited by morphine. Reversal of this antinociceptive effect of morphine during chronic treatment signalled the development of tolerance. Tolerance to morphine at the neuromuscular junction was shown as a reversal of the initial shift of the size of the excitatory junction potential (e.j.p.) vs extracellular calcium concentration relationship back towards the control without any change in the power of 2.4. Facilitation in the amplitude of the e.j.p. occurs with low frequency (2 Hz) stimulation. The initial increase in facilitation induced by morphine was reversed by chronic morphine treatment without any change in the plateau e.j.p. amplitude achieved after a long low frequency train of impulses. At high frequencies (10 Hz) the initial increase in e.j.p. amplitude was followed by a depression. Acute morphine administration decreased the size of the e.j.p., this was followed by an increase in facilitation and a decrease in depression. These effects were reversed after chronic morphine treatment. Tolerance to morphine involves a counteradaptive process which restores the normal entry of calcium ions or its actions within the release sites in promoting transmitter release.