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.

Effect of chronic morphine treatment on transmitter release from sympathetic varicosities of the mouse vas deferens

“…The increase in facilitation of the ej.p. amplitudes in response to stimulation by trains of impulses seen in acute morphine treatment was reduced after chronic morphine treatment (Einstein & Lavidis, 1984a (Einstein & Lavidis, 1984b). These results suggest that the probability of transmitter release by sympathetic varicosities was increasing during chronic morphine treatment (Einstein & Lavidis, 1984b).…”

“…amplitude does not occur if the preparation has been chronically morphine treated. This tolerance to morphine develops within 10 days of continuous morphine treatment (Einstein & Lavidis, 1984a) and is characterized by a shift of the relationship between e.'j.p. amplitude and [Ca2"]0 back towards the naive level.…”

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

“…Chronic exposure of release sites to morphine results in an adaptive response in which the excitability of the release sites is returned towards the control by the reversal of the above (Einstein & Lavidis, 1984).…”

“…On the sixth day the test was conducted 15 h after the last morphine dose. On the 10th day of morphine treatment the animals were injected with the scheduled morphine dose, 5-6 h later were killed by a cervical fracture and both vasa deferentia removed and prepared as previously described (Einstein & Lavidis, 1984 …”

“…(test impulse) divided by e.j.p. (conditioning or first impulse in a train) and was measured and quantified as described previously (Einstein & Lavidis, 1984).…”