Acute Tolerance to Narcotic Analgesic Drugs in Rats

Cox, B.; Ginsburg, M.; Osman, O.H.

doi:10.1111/j.1476-5381.1968.tb00986.x

Cited by 87 publications

(38 citation statements)

References 7 publications

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“…gesic effect of this alkaloid within a few hours, confirming the observation by Cox et al (1), and also obtained some evidences suggesting the similarity of the tolerance produced in this way to that routinely acquired by repeated administration (2).…”

supporting

confidence: 77%

A Simple Quantitative Method for the Evaluation of Physical Dependence Liability of Morphine in Mice

Kaneto

Nakanishi

1971

Jpn.J.Pharmacol

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Previously, we reported that a continuous infusion of morphine hydrochloride into mice either subcutaneously or intravenously could establish "acute tolerance" to the anal gesic effect of this alkaloid within a few hours, confirming the observation by Cox et al.(1), and also obtained some evidences suggesting the similarity of the tolerance produced in this way to that routinely acquired by repeated administration (2).On considering the well known intimate relationship of tolerance with physical de pendence, therefore, it would be the natural extension of our research to examine if the mice which developed distinct tolerance to morphine after a short-term infusion, had in deed become physically dependent on this alkaloid. In the same animal species implanted with morphine pellet, Way et al. (3) have recently succeeded in quantifying the intensity of developed physical dependence by estimating the dose of naloxone to precipitate with drawal jumping syndrome. In the experiment reported here, thus, we adopted the jump ing syndrome and the loss of body weight as the index of abstinence syndrome aiming at the evaluation of the intensity of physical dependence after continuous infusion of mor phine in mice. Adult male mice (dd-strain) weighing 20+0.5 g were used. The animal was fixed in a plastic box specially designed for this experiment and the solution of morphine hydro chloride (10 mg/ml) in saline was infused subcutaneously or intravenously at the rate of 35 mg/kg/hour using a continuous infusion apparatus (Natsume KN-204) which was modi fied so as to treat ten animals at one time. The details of the experimental condition ap plied for the present study have been reported previously (2). The mice which received saline instead of morphine solution served as control. After infusion for 1, 3, 5, 7 or 10 hours, the mouse was discharged from the box, weighed and transferred onto a circular platform (30 cm in diameter and 45 cm in height). The changes in body weight at inter vals of 30 minutes and the behaviour were recorded for the next three hours. Ten mg/kg

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supporting

confidence: 77%

A Simple Quantitative Method for the Evaluation of Physical Dependence Liability of Morphine in Mice

Kaneto

Nakanishi

1971

Jpn.J.Pharmacol

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“…The second component persists for many hours and represents tolerance (Christie et al, 1987). Interestingly, two phases of tolerance reversal have also been observed in vivo on cessation of chronic opioid administration (Cox et al, 1968).…”

Section: A Desensitization and Tolerance Are Both Associated With Rementioning

confidence: 95%

“…term tolerance for such prolonged exposure, qualified as "acute" (several hours, Cox et al, 1968) or "longterm" (days) to avoid confounding the mechanisms of rapid desensitization of MOR with potentially different mechanisms of tolerance.…”

mentioning

confidence: 99%

Regulation ofµ-Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance

et al. 2013

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“…Alternatively, tolerance can be defined as the need to increase the dose of a drug to maintain a response. Clinically, this often is seen over a period of days to weeks, but in animal models tolerance can be seen in rats in hours (Cox et al, 1968). A wide range of different and unrelated mechanisms impact tolerance, indicating that tolerance involves the convergence of many pathways to a common behavioral response.…”

Section: F Tolerance/dependence/withdrawalmentioning

confidence: 99%