Quantitative assessment of tolerance to and dependence on morphine in mice

Abstract

Tolerance to morphine-induced analgesia (hot plate and acetic acid whrithing test), hypothermia and lethality can be quantified in mice by measuring the degree of parallel shifts of semilog. dose-response relationships induced by repeated opioid administration. A similar procedure can be used for the quantification of naloxone-induced withdrawal as an indicator of dependence. The intensity of tolerance development with respect to time of administration and dosage of morphine varies with the test procedure. It is closely parallel, however, in both analgesic tests during acquisition of tolerance. Log-log-linear relationships exist between tolerance in analgesic tests and physical dependence as determined by naloxone-induced withdrawal. The minimum tolerance-inducing dose of morphine in different tests could not be correlated to the ED₅₀'s in these tests. Chronic opiate treatment leads to a decrease or an increase in motility response to morphine, depending on the time that has elapsed after the last morphine administration.