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Mechanisms of Tolerance to and Dependence on Narcotic Analgesic Drugs

Mechanisms of Tolerance to and Dependence on Narcotic Analgesic Drugs Doris H. Clouet and K. Iwatsubo1 New York State Drug Abuse Control, Commission Testing and Research Laboratory, Brooklyn, New York 11217 METHODS OF PRODUCING TOLERANCE AND DEPENDENCE IN LABORATORY ANIMALS Non-Primates Methods for evaluating the degree of tolerance to and/or dependence on narcotic analgesic drugs have been described in various reviews in this series and others (1-5). During the last five years, assays for tolerance and dependence have become quantitative and precise, especially in small laboratory animals. The daily administration of morphine or other opioids to rodents, cats, and dogs in one or more injections per day has been used for many years to produce the tolerant state wh!ch develops at a rate dependent on the specific drug, the dosage schedule, the interval between doses, and the sensitivity of the pharmacological assay (6). Another method of administering morphine to rodents has been described by Huidobro & Maggiolo, who implanted pellets of morphine base subcutaneously (7). The absorption of diug into the soft tissues from 100 mg pellets was uniform over a 30-day period during which tolerance developed (8). The formulation of the pellets was modified by Way and his colleagues by including various filler materials (9). The absorption http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Pharmacology and Toxicology Annual Reviews

Mechanisms of Tolerance to and Dependence on Narcotic Analgesic Drugs

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Publisher
Annual Reviews
Copyright
Copyright 1975 Annual Reviews. All rights reserved
Subject
Review Articles
ISSN
0362-1642
eISSN
1545-4304
DOI
10.1146/annurev.pa.15.040175.000405
pmid
238464
Publisher site
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Abstract

Doris H. Clouet and K. Iwatsubo1 New York State Drug Abuse Control, Commission Testing and Research Laboratory, Brooklyn, New York 11217 METHODS OF PRODUCING TOLERANCE AND DEPENDENCE IN LABORATORY ANIMALS Non-Primates Methods for evaluating the degree of tolerance to and/or dependence on narcotic analgesic drugs have been described in various reviews in this series and others (1-5). During the last five years, assays for tolerance and dependence have become quantitative and precise, especially in small laboratory animals. The daily administration of morphine or other opioids to rodents, cats, and dogs in one or more injections per day has been used for many years to produce the tolerant state wh!ch develops at a rate dependent on the specific drug, the dosage schedule, the interval between doses, and the sensitivity of the pharmacological assay (6). Another method of administering morphine to rodents has been described by Huidobro & Maggiolo, who implanted pellets of morphine base subcutaneously (7). The absorption of diug into the soft tissues from 100 mg pellets was uniform over a 30-day period during which tolerance developed (8). The formulation of the pellets was modified by Way and his colleagues by including various filler materials (9). The absorption

Journal

Annual Review of Pharmacology and Toxicology – Annual Reviews

Published: Apr 1, 1975

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