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Journal of Pharmacology And Experimental Therapeutics, Vol. 189, Issue 3, 759-771, 1974
Copyright © 1974 by American Society for Pharmacology and Experimental Therapeutics

MORPHINE PHYSICAL DEPENDENCE IN THE DOG

W. R. Martin 1, C. G. Eades 1, W. O. Thompson 1, J. A. Thompson 1, and H. G. Flanary 1

1 National Institute on Drug Abuse, Addiction Research Center, Lexington, Kentucky

A convenient procedure for making chronic spinal dogs physically dependent on morphine and maintaining them for many months has been described. Both the precipitated and withdrawal abstinence syndromes have been qualitatively described and quantitatively assessed and appear to be qualitatively different. The qualitative characteristics of the precipitated abstinence syndrome appear to depend on the level of dependence, whereas the withdrawal abstinence syndrome does not. The dependent spinal dog was used to assay the relative potencies of antagonists in precipitating abstinence. Good agreement was obtained between comparable data in man and estimates of antagonistic potencies obtained using the guinea-pig ileum. Morphine suppresses the withdrawal abstinence syndrome in a dose-related manner. Haloperidol was found to suppress certain signs of abstinence, but not others. Propranolol neither suppressed nor precipitated abstinence. The primary abstinence syndrome, characterized by increased pulse rate, pupillary diameter, respiratory rate and responsivity to nociceptive stimuli, became maximal on the 2nd day of withdrawal abstinence and persisted for about 1 week. A protracted syndrome then emerged characterized by a decrease in body temperature, slowing of pulse and respiratory rate, shortening of the latency of the skin twitch reflex, decreased responsivity of the flexor reflex to a low level of noxious stimuli and increased responsivity to medium and high strengths of stimuli. The relationship between these findings and exacerbation of the psychopathic personality as a consequence of narcotic addiction is discussed.

Submitted on October 4, 1973
Accepted on February 12, 1974




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[Abstract] [Full Text]


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Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics.