Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era
Background to An Oral History of the First Fifty Years
Addiction (Volume Six): 4a. Contributions of interviewees
(Bulletin 57)

            Volume Six covers the first 50 years in the developments of the neuropsychopharmacology of addiction (Ban 2011a; Kleber 2011).

            Of the 22 interviewees included in this Volume, three (Noble, O’Brien and Schoolar) are MD, PhDs; 11 (Blaine, Charalampous, Jaffe, Jasinsky, Kleber, Klee, Kreek, Meyer, Primm, Schuckit and Volkov) are MDs; and eight (Adler, Barry, Kornetsky, Pickens, Schuster, Way, Wayner and Woods) are PhDs. Of the 14 MDs, all but one (Kreek) are psychiatrists. Of the PhDs, including MD, PhDs, six (Barry, Kornetsky, Pickens, Schuster, Wayner and Woods) received their degree in psychology; two (Adler and Schoolar) in pharmacology; and of the remaining three Noble received his degree in biochemistry, O’Brien in neurophysiology and Way in pharmaceutical chemistry. 

            All but four interviewees (Blaine, Jasinsky, Pickens and Primm) are affiliated with the American College of Neuropsychopharmacology (ACNP). The 18 ACNP members include two founders (Klee and Kornetsky) and two past presidents (Meyer and O’Brien).  

            The interviews were conducted from 1995 to 2009 and, with the exception of five (Blaine, Jasinsky, Klee, Pickens and Primm), were done at ACNP’s annual meetings. Blaine, Jasinskyand Pickens were interviewed in Washington, DC; Klee in Baltimore; and Primm in Orlando, Florida.

            The 22 interviewees were interviewed by 14 interviewers. Twelve of the interviewers were peers of the interviewees, knowledgeable in the same field, and two (Campbell and Tone) were medical historians. Ten of the interviewers (Campbell, Carpenter, De Lisi, Gold, Koob, Kosten, London, O’Brien, Sanberg and Stein) conducted one interview and four conducted multiple interviews, i.e., two (Healy and Tone), four (Ban) and five (Hollister).  One of the interviewees (O’Brien) was interviewed by two interviewers (Hollister and Ban). 

            By the time Volume 6 was published, one of the interviewers (Hollister) passed away (Ban 2011b).

Contributions of Interviewees

            The 22 interviewees were involved in six broadly defined areas of research related to the neuropsychopharmacology of addiction. Many of them were also involved in the social – political arenaof addiction. In fact, the most important contribution of one of the interviewees, Benny J. Primm, was the organization of clinical services, including methadone clinics for addicts in the black population of the United States in the 1970s and ‘80s (Primm 1992; Primm, Cook and Drew 1981).

            Three of the interviewees (Adler, Meyer and Wood) contributed to defining the biological properties of addiction. E. Long Way, in his life-time research from the 1960s to the ‘90s, presented evidence that “tolerance” and “dependence” have a common biochemical basis. He demonstrated an increase of norepinephrine (NE) release in both (Way 1993; Way, Leoh and Schen 1968).

            In the late 1970s Roger E. Meyer reported that the subjective state associated with “craving” was rewarding and not aversive (Meyer and Mirin 1979).Meyer was among the first to demonstrate, in the 1980s, a significant interaction between psychiatric diagnosis (psychopathology) and treatment outcome in alcoholism (Rounsavi, Dolinsky, Babor and Meyer 1987).

            In the early 1960s Martin W. Adler discovered that rats with chronic brain lesions have increased sensitivity to amphetamines (Adler 1961).He referred to the phenomenon as “denervation super-sensitivity,” adopting the term coined by Cannon in the late 1940s (Cannon 1949).In the late 1990s, Adler was a member of the team that discovered chemokine receptors in a subset of neurons (Horuk, Martin, Wang et al. 1997).He suggested that chemokines represent a third transmitter system in the brain and was first to study chemokines in drug addiction (Adler, Geller, Chen and Rogers 2006).

            Six of the interviewees (Barry, Kornetsky, O’Brien, Pickens, Schuster and Woods) were involved with conditioningresearch in addiction. Charles O’Brien was first, in 1979, to demonstrate conditioned narcotic withdrawal in humans (O’Brien, Testa, O’Brien, Brady and Wells 1979).In the same year he had also shown conditioned limbic system activation in craving (Childress, Mozley, McElgin, Fitzgerald, Reivich and O’Brien 1999).In 1992, O’Brien was member of the team that reported on the effectiveness of naltrexone in alcoholism (Volpicelli, Alterman, Hayashida and O’Brien 1992). He was also a member of the team, in the early years of the 21^st century, which  found that a functional polymorphism of the µ opioid receptor gene was associated with responsiveness to naltrexone in alcoholic patients (Oslim, Barrettin, Kranzler et al.2003).

            Conan Kornetsky was among the first to show, in the 1970s and ‘80s,that both morphineand alcoholincrease sensitivity for rewarding brain stimulation (Bein and Kornetsky 1989; Esposito and Kornetsky 1978). In the 1990s, he demonstrated that in the reinforcing effect and abuse of substances, the nucleus accumbens and olfactory tubercle play a roleand provided evidence that dopamine was a common substrate in the rewarding effect of brain stimulation for cocaine and morphine (Kornetsky and Douvachelle 1994; Kornetsky, Houston, Lyons and Perrino 1994).

            Charles R. Schuster was first in the mid-1960s to show that a stimulus associated with nalorphine administration could elicit signs of withdrawal in morphine dependent monkeys. (Goldberg and Schuster 1967).During the 1960s, Schuster developed animal models of self-administrationand demonstrated that drugs can be used as “reinforcers” in monkeys and man (Johanson and Schuster 1981; Schuster 1976; Thompson and Schuster 1965).  In the 1970s, in collaboration with Marian A. Fishman and others, Schuster found a relationship between plasma concentration and the subjective and physiological (cardiovascular) effects of cocaine (Fischman, Schuster, Resnekov, Schick and Krasnegor 1976; Javaid, Fischman, Schuster et al. 1978).

            In the late 1960s, James H. Woods, in collaboration with Steven R. Goldberg and Schuster, was first to show conditioned increases in self-administration of morphine in monkeys (Goldberg, Woods and Schuster 1969). In 1981, in collaboration with Young and Herling, Woods reported that history of drug exposure was a “determinant” of drug self-administration (Young, Herling and Woods 1981).During the 1970s Woods measured narcotic tolerance by a “shift to the right” in dose-effect relations in operant behaviour (Woods and Carney 1978).

            In the 1970s Roy Pickens had shown that drugs of abuse in human are self-administered by animals (Pickens 1977). In the 1980s, he demonstrated that personality factors play a role in drug “self-administration” in humans(Pickens and Heston 1981).

            Herbert Barry III was first to employ drug-effects as discriminative stimuli in the differentiation of drugs of abuse. In 1972, in collaboration with R.K. Kubana, he published on the stimulus characterization of cannabis components and demonstrated the discriminative effect of δ-9-tetrahydrocnnabinol (Kubana and Barry 1972).Barry classified drugs according to their discriminative effects in ratsand, in collaboration with Krimmer, he described the differential stimulus attributes of chlordiazepoxide and pentobarbital (Barry 1974; Barry andKrimmer 1979). 

            One of the interviewees, Nora Volkow, contributed to the detection of structures involved in addiction with functional brain imaging. In the late 1990s Volkow reported on decreased striatal dopaminergic responsiveness in detoxified cocaine dependent subjectsand in the early years of the 21^st century she had shown the involvement of the frontal cortex in addiction (Goldstein an\d Volkow 2002; Volkow, Wang, Fowler et al. 1997).

References:

Adler MW. Changes in sensitivity to amphetamine in rats with chronic brain lesions. The Journal of Pharmacology 1961; 134: 214-21.

Adler MW, Geller EB, Chen X, Rogers TJ. Viewing chemokines as a third major system of communication in the brain. AAPS Journal 2006; 7: 65-70.

Ban TA, editor. An Oral History of Neuropsychopharmacology. The first Fifty Years. Peer Interviews. Volume 6 (Kleber HD, editor, Addiction). Budapest: Animula; 2011a.

Ban TA. Preface. In Kleber HD, editor. Addiction. (Ban TA, editor. An Oral History of Neuropsychopharmacology. The first Fifty Years. Peer Interviews. Volume 6.) Budapest: Animula; 2011b, pp. ix-xxvi.

Bain GT, Kornetsky C. Ethanol oral self-administration and rewarding brain stimulation. Alcohol 1989; 5: 499-503.

Barry H III. Classification of drugs according to their discriminative effects in rats.  Fed Proc 1974; 33: 1814-24.

Barry H III, Krimmer EC. Differential stimulus attributes of chlordiazepoxide and pentobarbital. Neuropharmacology 1979; 18: 991-8.

Cannon WB. The Supersensitivity of Denervated Structures. New York: Macmillan; 1949.    

Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O’Brien CP. Limbic activation during cue-induced cocaine craving. Am J Psychiatry 1999; 156: 11-8.

Fischman MW, Schuster CR, Resnekov L, Shick JFE, Krasnegor NA.  Cardiovascular and subjective effects of intravenous cocaine administration in human. Arch Gen Psychiatry 1976; 33: 983-9.

Goldberg SR, Schuster CR. Conditioned responses by a stimulus associated with nalorphone in morphine-dependent monkeys. J Exp Anal Behav 1967; 10: 235-42.

Goldberg S, Woods JH, Schuster CR. Morphine: conditioned increases in self-administration in monkeys. Science 1969; 166: 13-6.

Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 2002; 159: 1642-52.

Esposito RU, Kornetsky C. Morphine increases sensitivity to rewarding brain stimulation. Neuroscience and Biobehavioral Research 1978; 2: 110-22.

Horuk R, Martin AW, Wang Z, Schweitzer L, Gerassimides A, Guo H, Lu Z, Hesselgesser J, Perez HD, Kim J, Parker J, Hadley TJ, Peiper SC.. Expression of chemokine receptors by subsets of neurons in the central nervous system.. J Immunology 1997; 158: 2882-90.

Javaid JI, Fischman MW, Schuster CR, Dekirmenjian H, Davis JM.. Cocaine plasma concentration: relation to physiological and subjective effects in humans. Science 1978; 202: 227-8.

Johanson CE, Schuster CR. Animal models of self-administration. In: Mello NK, editor. Advances in Substance Abuse: Behavioral and Biological Research. Volume 2. Connecticut: JAJ Press; 1981, p. 219-97.

Kleber HD, editor. Addiction. In: Ban TA, editor. An Oral History of Neuropsychopharmacology. The first Fifty Years. Peer Interviews. Volume 6. Budapest: Animula; 2011.

Kornetsky C, Houston-Lyons D, Porrino LJ. The role of nucleus accumbens and olfactory tubercle in the effect of morphine in rats exposed to escapable foot-shock. Brain Research 1994; 663: 303-11.

Kubana RK, Barry H III. Stimulus characterization of marihuana components. Nature 1972; 235: 397-8.

Meyer RF, Mirin SH. The Heroin Stimulus. New York: Plenum Press; 1979.

O’Brien CP, Testa T, O’Brien TJ, Brady JP, Wells B. Conditioned narcotic withdrawal  in human. Science 1979; 195; 1000-2.

Oslin DW, Barrettini W, Kranzler HR, Pettinati H, Gelertner J, Volpicelli JR, O’Brien CP. A functional polymorphism of the µ opioid receptor gene is associated with naltrexone response in alcohol dependent  patients. Neuropsychopharmacology 2003; 28: 1546-52.

Pickens R. Behavior pharmacology. A brief history. In: Thomson T, Dews PB, editors. Advances in Behavior Pharmacology. New York; Academic Press; 1977, p. 229-57.

Pickens R, Heston LL. Personality factors in human self-administration. NIDA Research Monographs 1981; 37: 45-62.

Primm BJ. Alcohol and other drug abuse: changing lives. Therapy, research and teaching. Journal of Health Care for the Poor and Underserved. 1992; 3: 1-17.

Primm BJ, Cook DR, Drew J. The problem of addiction in the black community. In: Lowinson JH, Ruiz P, editors. Substance Abuse. Clinical Problems and Perspective. Baltimore: Williams & Wilkins; 1981. 

Rounsaville B J, Dolinsky ZS, Babor TF, Meyer RE. Psychopathology as a predictor of treatment outcome in alcoholism. Arch Gen Psychiatry 1987; 44: 505-13.

Schuster CR. Drugs as reinforcers in monkeys and man. Psychopharmacology Reviews 1976; 27: 511-21.

Thompson T, Schuster CR. Behavior Pharmacology. Englewood Cliffs (NJ): Prentice Hall; 1968.

Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP. Naltrexone in the treatment of alcoholism. Arch Gen Psychiatry 1992; 49: 876-80.

Way EL. Opioid tolerance and physical dependence and their relationship. In: Herz A, ed. Handbook of Experimental Pharmacology 1993; 104: 1573-96.

Way EL, Leoh HH, Schen FH. Morphine tolerance, physical dependence and synthesis of brain 5-hydroxytryptamine. Science 1968; 162: 1290-2.

Volkow ND, Wang G-J, Fowler JS, Legan J, Gatley SJ, Hitzeman R, Chen D, Dewey SL, Pappas N. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 1997; 386: 830-3.

Woods JH, Carney J. Narcotic tolerance and operant behavior. NIDA Research Monograph 1978; 18: 54-66.

Young AM, Herling S, Woods JH. History of drug administration is a determinant of drug self-administration. NIDA Research Monographs 1981; 37: 75-89.

February 14, 2019