R.I.P. Charles Robert Schuster, Ph.D.

February 23, 2011

An towering figure of the substance abuse research fields has passed away. According to a note posted to an ASPET mailing list, Charles Robert Schuster, Ph.D. suffered a fatal stroke on Feb 21 in Houston Texas. NIDA Director Nora Volkow has also posted a notice to the NIDA-grantees mailing list.
The CPDD biography of Dr. Schuster is a brief overview of his career.

After six years in the Department of Pharmacology at the University of Michigan, he joined the Departments of Psychiatry, Pharmacology, and Behavioral Sciences and founded the University of Chicago´s Drug Abuse Research Center. In 1986, Dr. Schuster was appointed the Director of the National Institute on Drug Abuse, a position he held until 1992. In January of 1995, Dr. Schuster was appointed as a Professor in the Department of Psychiatry and Behavioral Neurosciences at Wayne State School of Medicine and the Director of the Substance Abuse Research Division.

ResearchBlogging.orgOne of the most fundamental and lasting advances of Dr. Schuster was the development of the self-administration model of drug reinforcement. Bob Schuster was one of the first to demonstrate that animals would work to receive intravenous infusions of drug and he was a major player in several of the initial observations on the reinforcing properties of recreational drugs through the 1960s and 1970s.
James R. Weeks published in 1962 that female rats would press a lever to receive intravenous infusions of morphine. Schuster and his colleagues were the first to adapt this method to nonhuman primates, getting started at approximately the same time as Weeks (there are references to Abstract presentations from Weeks as early as 1960 or 1961).

Clark, Schuster and Brady (1961) implanted two rhesus monkeys with internal jugular vein catheters and demonstrated that the monkeys would press a telegraph key for saline infusions. Furthermore, the provision of drinking water to the animals decreased the amount the monkeys would press the key, suggesting that this behavior was sensitive to “drive” (this term for motivation was popular then). The authors quite naturally speculated that this model would be useful for “experimental analysis of the reinforcing properties of many pharmacologic agents”. Was it ever
Thompson and Schuster (1964) reported that rhesus monkeys would work for intravenous infusions of morphine. This report references a “Technical Report” of their own dated July of 1962, for priority purposes one assumes :-). In the first experiment, three male rhesus monkeys were made dependent on morphine by means of four daily injections (7 mg morphine sulfate per kg bodyweight ) for 30 days. Thereafter, the monkeys were trained on a Fixed Interval-Fixed Ratio chained schedule in which they first had to complete an FI2min (first response after 2 min) to produce a stimulus light during which a FR25 (25th response completed ratio) was in place to obtain a morphine infusion. In this experiment the per-reinforcer dose available every 6 hrs (7 mg/kg) was the same as that used to induce dependence. The experimenters then showed that 24 hr discontinuation (after establishing stable responding) resulted in an increased response rate during the FI and decreased latency to complete the FR when drug was again available. Likewise, pretreatment with the opiate antagonist nalorphine also increased FI responding and speeded completion of the FR. Finally, a pre-session injection of morphine decreased the behavioral output for self-administered morphine as a function of the pre-session morphine dose. In short, they had provided the necessary demonstration that monkeys would “work for drug”, showing that it functioned as a reinforcer in the classical operant behavioral paradigm.
This work had a lasting and substantial influence on the course of laboratory research on the reinforcing properties of drugs, as well as the brain mechanisms (structural, chemical, physiological) that were involved in reward and reinforcement. Drug mediated or otherwise. A PubMed search for “(rhesus OR macaque OR saimiri) AND (self-injection OR self-administration)” pulls up 769 references which can all be attributed to the methodological and experimental work of Dr. Schuster in the early 1960s. Many of these papers are authored by Dr. Schuster and his immediate colleagues and trainees. Unfortunately the Neurotree entry for Charles Schuster is woefully underpopulated. I was hoping to give you a sense of the degree to which he is the scientific father, grandfather and likely great-grandfather of so many people who have made seminal observations in substance abuse. Perhaps the field will be encouraged to complete this tree as a tribute to his professional life.
Dr. Volkow’s email referenced one of Dr. Schuster’s findings that anticipated, by at least a decade, a novel approach to therapy for drug abuse. I mentioned vaccination for cocaine abuse here and here. In the latter post I mentioned an attempt in the late 1970s to generate immunizations against opiate dependence. Yes, this was the work of Dr. Schuster. Bonese and colleagues (1974) trained a rhesus monkey to self-administer heroin or cocaine (on alternate days). Following immunization with a conjugate vaccine that produced antibodies capable of binding morphine, the monkey self-administered the same amount of cocaine as before, but wouldn’t work for heroin. Increasing the per-infusion dose in steps, it was found that a 16-fold increase in per-infusion dose was required to restore self-administration. The animal thereafter reached an intake level of drug in the 2 hour session that was about 10-fold higher than the pre-immunization baseline. These studies anticipated a series of cocaine-vaccination studies in rats in the early 1990s that has then generated a more or less continual body of research into vaccines for cocaine, nicotine and methamphetamine abuse/dependence. Clinical trials are ongoing for cocaine and nicotine vaccines.
These are but two of the methodological and scientific veins that owe their origins in large part to the efforts of Dr. Schuster. There are his many, many trainees and academic descendants who are perhaps an equally important part of his legacy. I have not even touched upon his tenure as the Director of NIDA with the concomitant influence he had upon drug-abuse science in that role.
Suffice it to say that Dr. Schuster contributed greatly during his professional lifetime to our understanding of substance use, abuse and dependence. For that we are grateful and we celebrate the contributions of this scientist.
Clark, R., Schuster, C., & Brady, J. (1961). Instrumental Conditioning of Jugular Self-Infusion in the Rhesus Monkey Science, 133 (3467), 1829-1830 DOI: 10.1126/science.133.3467.1829
Bonese KF, Wainer BH, Fitch FW, Rothberg RM, & Schuster CR (1974). Changes in heroin self-administration by a rhesus monkey after morphine immunisation. Nature, 252 (5485), 708-10 PMID: 4474602

3 Responses to “R.I.P. Charles Robert Schuster, Ph.D.”

  1. Matt B Says:

    There are a couple of nice interviews with Schuster available on the web that not only give a sense of how central he is to behavioral pharmacology (writing the first textbook, for example) but also convey his warm and generous personality.


  2. DrugMonkey Says:

    Thanks for the links Matt. As you say, they help to convey a sense of the man behind the accomplishments.


  3. Abel Says:

    Here’s another one, Drug and Matt:
    Schuster describes how his mom was a jazz musician and his own forays into music put him close to folks doing a lot of drugs. It scared him out of music and into substance abuse research.
    He sounds like a remarkable man and scientist. I’m sorry to have never met him.


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