and opiate receptors. This knowledge is consid- 

 ered fundamental for elucidating the molecular 

 mechanisms involved in drug addition. Among the 

 major contributors in endorphin research are: 



• Goldstein, Avram, "Biochemical Mechan- 

 isms in Drug Addiction" 



• Simon, Eric, "Effects of Morphine and Ana- 

 logues on Cell Metabolism" 



• Snyder, Solomon H., "Johns Hopkins Drug 

 Abuse Research Center" 



• Kosterlitz, Hans and John Hughes, "Narcot- 

 ic Antagonists: Assessment and Mode of 

 Action" 



• Way, Eddy Leong, "Narcotic Tolerance and 

 Physical Dependence Mechanisms." 



Other important basic research contributions by 

 NIDA-funded scientists include: 



• Ralph Mechoulam's discovery of the active 

 ingredient in marihuana, delta-9-THC. 



• Daniel Freedman's work in elucidating the 

 mechanisms of action of hallucinogens. 



• Maurice Seevers" development of an animal 

 model for determining the abuse liability of 

 drugs. 



• Abraham Wikler's pioneering definition of 

 drug abuse in behavioral terms. 



• Gabriel Nahas' description of the effects of 

 THC on DNA, metabolism, and on hormone 

 and immune systems. 



Although NIDA's research program is primarily 

 extramural, much important research has been 

 conducted at the Addiction Research Center in 

 Lexington, Kentucky, which conducts the intra- 

 mural programs of NIDA. Contributions made in 

 research at the Center include: 



• Identification of a long-lasting partial agonist 

 of the morphine type. Quite recently, some 

 exciting properties of a new analgesic, bu- 

 prenorphine, have been identified. These may 

 make it not only an especially useful analge- 

 sic but also suggest that it has value for 

 treatment. This agent is a partial agonist of 

 the morphine type with a ceiling effect equiv- 

 alent to about 20 mg. of morphine. It appears 

 to have a very long duration of action. 



• The discovery that naloxone is a pure antag- 

 onist in man. Naloxone has been shown to 

 have essentially no pharmacologic activity in 

 man other than antagonizing the actions of 

 morphine and, when it is administered chron- 

 ically, it does not produce physical depend- 

 ence. 



• Receptor identification. Three separate recep- 

 tors have been identified that contribute to 

 the actions of narcotic analgesics and related 

 compounds. These three receptors are re- 

 spectively responsible for the euphorigenic, 

 sedative, and dysphoric and hallucinogenic 



effects of this general class of drugs. 



• Addiction and hypophoria. An hypothesis 

 has been put forth that states that the funda- 

 mental pathology of addicts and alcoholics is 

 a defect which results in an increased "need' 

 state and feelings of hypophoria. The feel- 

 ings of hypophoria may be directly related to 

 the increased "need" state and are partly 

 reactive. These give rise to the impulsivity 

 and egocentricity that characterize much of 

 the addict's pathological social behavior. In 

 this regard, it has been demonstrated that 

 addicts and alcoholics have elevated levels of 

 both testosterone and luteinizing hormones. 



NIMH 



Research in the extramural program is usually 

 investigator-initiated and thus reflects the state of 

 knowledge and interests of scientists studying 

 behavioral and mental health/illness issues and 

 problems. The following list provides examples of 

 significant projects supported in the past 10 years 

 but cannot reflect the breadth of the extramural 

 program . 



• Lynch, Gary, "Psychobiological Studies of 

 Neuronal Plasticity." This work demonstrat- 

 ed that damaged tissue with the central nerv- 

 ous system (hippocampus) can regenerate. 

 The sprouting observed in afferent fibers 

 subsequent to a lesion may account for be- 

 havioral plasticity and postulated memory 

 mechanisms. 



• Sperry, Roger, "Investigation of Neural 

 Mechanisms in Behavior." This research 

 extended and elaborated the notion of hemi- 

 spheric specialization and the complementary 

 modes of central processing in the two hemi- 

 spheres of the brain. This work is considered 

 basic to the possible determination of the 

 cerebral organization necessary for psycho- 

 logical characteristics. 



• Grossman, Sebastian, "Role of Subthalamic 

 Mechanisms in Ingestion." Different motivat- 

 ed behaviors — i.e., eating or drinking — were 

 elicited in sated animals by direct injection of 

 different chemicals at the same hypothalamic 

 site. This series of studies, which makes use 

 of both lesions and neurotransmitters to man- 

 ipulate the nervous system, is basic to the 

 understanding of the central mechanisms that 

 organize ingestive behavior in accordance 

 with physiological requirements. 



• Estes, William, "Feedback Processes in Pun- 

 ishment and Reward." The theoretical model 

 resulted from a series of animal and human 

 learning experiments integrated within a 

 common set of constructs, theories, and 

 models which accounted for limited amounts 



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HEALTH, EDUCATION AND WELFARE 



