Sixteen opioid agonists were studied for their capacity both to maintain responding previously reinforced by codeine and to suppress the withdrawal syndrome induced by morphine deprivation in rhesus monkeys. All compounds, which included examples from each of the major chemical families of opioids, maintained responding at rates above those maintained by saline. There were differences among the compounds in the maximal response rates maintained, and large differences in their potencies in maintaining responding. In morphine-dependent monkeys, the abstinence signs that developed 14 h after the last morphine dose were suppressed completely by all of the compounds except codeine. There was a strong positive correlation (r = 0.92) between the potency of a compound in maintaining drug-reinforced responding and the potency of the compound in suppressing the morphine withdrawal syndrome.
FIVE YEARS ago, I inherited from my predecessor a colony of 'junkie monkeys', Macca mulatta rhesus monkeys that are kept physically dependent by gwmg them morphine sulfate, 3 mg/kg subcutaneously four umes each day. For the past 25 years, this monkey colony has been used to evaluate the physical dependence habiilty of drugs of the morphine family. The colony has been one part of a structure, designed and operated by the late Nathan B. Eddy, for the purpose of keeping off the American market any dangerous, new addictive drugs. The American people, fnghtened for many years by the spectre of the drug-crazed dope fiend, is wdhng, from Ume to Ume, to give pohUcal support to programs for the control of drug abuse. Nathan B. Eddy created such a program. It flourished dunng the 1930's but perished in the early 1940's during World War II. Immediately after that war, because of the knowledge that the Germans had invented mependme (pethldme), methadone and perhaps many other potent narcoUc analgesics, Eddy's program was re-established and expanded. A committee, now known as the Committee on Problems of Drug Dependence, was estabhshed as an arm of our Nauonal Academy of Sciences-National Research Council (NAS-NRC). For all pracUcal purposes, Eddy was the Committee on Problems of Drug Dependence In the name of the Committee, he collected money from pharmaceutical industry to support research acuvmes. Over a period of two decades, much of that research money went to Ann Arbor, .M|chigan, where Maunce H. Seevers used it to estabhsh and mmnta|n a colony of morphmedependent monkeys. The primary purpose of this colony was to prevent the overloading of the colony of human volunteer addicts at the Addicuon Research Center at Lexington, Kentucky. By screening drugs first at Michigan, It was possible to channel the human resources to the most interesting and important drugs. In order for a new drug (narcoUc or otherwise) to be admitted to the Amencan market, it must first be approved by our Food and Drug AdministraUon. In the case of a narcotic drug, the FDA would not approve a drug unless it had been tested and recommended by the Lexington group. Lexington would not examine a new drug unless it had been evaluated for its physical dependence habillty at the Michigan facility. This chmn of evaluations was superwsed by the Committee on Problems of Drug Dependence. In pracUce, a manufacturer wanting approval of a new narcot|c drug would submit a sample of it to the Committee, where Eddy (or his successors) would perform an analgesic evaluauon using the mouse hot-plate test. Then some of the drug would be sent to Seevers at Michigan. It would be ]denufied only by a code number and it would be accompamed by only a recommended starting dose and, occasionally, by suggestmns for solubillzing the material Thus, Seevers and his colleagues never knew the source of a tested compound, ItS chem|cal structure, ~ts metabolic fate or any other such mformaUon at the Ume that the drug was being tested. The tests now used at The University of Michigan ar...
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