Physical Dependence In Mice Research Articles

Significance of withdrawal jumping response in predicting physical dependence in mice.

The significance of the naloxone-induced jumping response in predicting the physical dependence capacity of morphine-like analgesics was investigated in mice treated with morphine, morphine-6-glucuronide and pentazocine. The jumping response was induced by naloxone in mice chronically treated with morphine and morphine-6-glucuronide, but its development is not necessarily related to the number or frequency of drug injections, and it was also observed even after a single dose of the drugs. The jumping was not precipitated in mice chronically treated with pentazocine. The naloxone-induced jumping response in mice treated with morphine was not masked by morphine, but was markedly suppressed by chlordiazepoxide, diazepam, methamphetamine, delta-9-tetrahydrocannabinol and diphenylhydantoin. It is concluded that the naloxone-induced jumping response is not a specific abstinence phenomenon in mice treated with morphine-like analgesics, although it may be used for a first screening test to estimate a physical dependence capacity.

Significance of Withdrawal Jumping Response in Predicting Physical Dependence in Mice*

The significance of the naloxone-induced jumping response in predicting the physical dependence capacity of morphine-like analgesics was investigated in mice treated with morphine, morphine-6-glucuronide and pentazocine. The jumping response was induced by naloxone in mice chronically treated with morphine and morphine-6-glucuronide, but its development is not necessarily related to the number or frequency of drug injections, and it was also observed even after a single dose of the drugs. The jumping was not precipitated in mice chronically treated with pentazocine. The naloxone-induced jumping response in mice treated with morphine was not masked by morphine, but was markedly suppressed by chlordiazepoxide, diazepam, methamphetamine, delta-9-tetrahydrocannabinol and diphenylhydantoin. It is concluded that the naloxone-induced jumping response is not a specific abstinence phenomenon in mice treated with morphine-like analgesics, although it may be used for a first screening test to estimate a physical dependence capacity.

Tolerance to Opioid Narcotics: Time Course and Reversibility of Physical Dependence in Mice

REPEATED administration of an opiate narcotic leads to the tolerant-dependent state. Previous communications1,2 from this laboratory have described the relationship between the degree of tolerance in mice and the dose, interval and duration of exposure to an opiate. Recently, jumping behaviour elicited by the opiate antagonist, naloxone, was shown to be a sensitive indicator of the degree of dependence3. We have used this method to follow the time courses of the onset and reversal of dependence in various conditions of exposure to opiates.

PHARMACOLOGICAL STUDIES ON ANAGESICS: REPORT 5: DEVELOPMENT OF PHYSICAL DEPENDENCE IN MORPHINIZED MICE

Addiction to morphine is a problem widely studied but not yet solved. One of the difficulties of this problem is that it involves physical and psychic factors and it is believed that these signs can be demonstrated only in vertabrates with highly developed cerebral hemispheres. Consequently, addiction experiments in animals have been carried out with higher animals, such as man, monkey, chimpanzee and dog. However, it has been recently reported that rats dosed morphine at 12 hours intervals for several weeks show signs of physical dependence to morphine (1-5). However, we have as yet very little information as to the possibility that similar signs can be also demonstrated in mice. A study of addiction or physical dependence in mice as compared with rats, namely the species difference between mice and rats in their response to morphine, is of great importance for the elucidation of the mechanism of the action of analgesics. The present paper deals with the development of tolerance to and the occurrence of physical dependence to morphine in mice.