DURING my investigation of the tolerance for morphine and codeine using ‘coughing dogs’1, I noted that acquired tolerance for these drugs by which their antitussive effects were completely lost was reduced or eliminated by an electric shock or a cardiazol shock. Morphine (2–6 mgm./kgm.) given intravenously completely depressed coughing for 1–6 hr. in such dogs on the first day of administration. By continued daily application of the drug, the dogs acquired tolerance in five to ten days; but the same drug failed to depress coughing afterwards. Similar tolerance for codeine developed in eight to fourteen days. The dogs thus made tolerant for morphine or codeine were subjected to an electric shock (a.c. 90–100 V., 2 sec.) or cardiazol shock (30–50 mgm./ kgm.). On the following day, each antitussive drug was one-fourth to three-fourths as potent, or in a few cases, quite as potent, as on the first day of administration, indicating that the shock had reduced or eliminated the tolerance.
Kasé, Y., Jap. J. Pharmacol., 4, 130 (1955).
Goldman, E. E., “Vitalfarbung am Zentralnervensystem”, (Georg Reimer, Berlin, 1913).
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KASÉ, Y. Effect of Electric Shock and Cardiazol Shock on Morphine Tolerance. Nature 177, 1136 (1956). https://doi.org/10.1038/1771136a0
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