PT  - JOURNAL ARTICLE
AU  - Martin, W. R.
AU  - Eades, C. G.
TI  - DEMONSTRATION OF TOLERANCE AND PHYSICAL DEPENDENCE IN THE DOG FOLLOWING A SHORT-TERM INFUSION OF MORPHINE
DP  - 1961 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 262--270
VI  - 133
IP  - 2
4099  - http://jpet.aspetjournals.org/content/133/2/262.short
4100  - http://jpet.aspetjournals.org/content/133/2/262.full
SO  - J Pharmacol Exp Ther1961 Aug 01; 133
AB  - An 8-hour infusion of morphine has been used to produce a demonstrable degree of physical dependence and tolerance in the dog. Physical dependence has been unmasked by nalorphine and the syndrome produced by this procedure is distinct, reproducible, and consists of restlessness, apprehension, violent tremors, lacrimation, salivation, rhinorrhea, urination, defecation, vomiting, mydriasis and tachycardia. Tolerance is readily discernible during the course of infusion and can be clearly demonstrated the day following infusion, using a standard test dose of morphine. Tolerance to behavioral depression (narcosis), depression of the skin twitch, and withdrawal reflex is marked. The reproducibility and brevity of this method may recommend it for preliminary screening of analgesic agents to identify those that produce physical dependence. 1961 by The American Society for Pharmacology and Experimental Therapeutics