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): 3. Conditioning and addiction 
( Bulletin 56) 



            Recognition by the 1950s that conditioning, classical or operant, plays a role in the pathogenesis of addiction, lead to the identification of brain structures and biochemical substrates involved in addiction. The signal difference between the two paradigms of conditioning is that in classical conditioning the establishment and retention of conditioned reflex (CR) depends exclusively on the associated administration of the conditioned and unconditional stimuli, whereas in instrumental conditioning, a third factor, reward or punishment, that follows the reflex also plays a role (Ban 1964, 1966). 

            The roots of the instrumental paradigm of conditioning are in Edward Thorndike’s recognition in 1911 that some behavior is regulated by its consequences. Miller and Konorski were first, in the late 1920s, to describe what was to become the instrumental paradigm of conditioning, in which the establishment and retention of a CR depended on reward or punishment that followed the reflex (Miller and Konorski 1928; Thorndike 1911). From the two modern learning theories, “contiguity theory” is based on the classical paradigm and “reinforcement theory” on the instrumental. For Edward Ray Guthrie and Edward C. Tolman the basic condition necessary for learning is that of contiguity of experience (Guthrie 1930, 1934; Tolman 1932, 1936). For Clark L. Hull drive reduction is crucial. If in the course of trial and error responses the organism performs the response that is associated with the reduction of motivation, the probability increases that the response will occur again under similar conditions. In Hull’s “law of effect,” drive reduction is the “principle of reinforcement” (Hull 1929, 1930, 1943). 

            In the mid-1930s, H. Schlossberg demonstrated that involuntary visceral reactions, mediated by the autonomic nervous system, follow the principle of association or “sheer contiguity,” whereas voluntary “precise adaptive responses” of the skeletal muscles follow the principle of success or reinforcement (Schlossberg 1934, 1936, 1937). Schlossberg’s “two-factor theory” was further elaborated by Burrhus Frederic Skinner, who introduced the term “operant behavior” and replaced the term “instrumental conditioning” with the term “operant conditioning.” For Skinner, the difference between the two paradigms of conditioning is that in “operant conditioning” the animal only receives the reinforcing, rewarding stimulus, if it does something, e.g., operates a lever (Hilgard and Marquis 1940). He argues that a stimulus is reinforcing if it strengthens the response that precedes it regardless whether it satisfies a drive (Skinner 1931, 1936, 1938).    

            In the early 1950s Delgado, Roberts and Miller at Yale University began work on learning and electrical brain stimulation. They found that stimulating a number of areas deep in the brain made the animals react if they were in pain. The animal could be taught to avoid an electrical stimulation in the area of its brain associated with pain as it could be conditioned to avoid a painful stimulus to the body (Delgado, Roberts and Miller 1954). In 1954, the same year Delgado and his associates published their findings, James Olds and Peter Milner at McGill University reported that they found areas in the brain where electrical stimulation was sought by the rat (Olds and Milner 1954). With electrodes implanted in the septal area, one of the “pleasure centers,” some rats in Olds’ experiments stimulated themselves as often as 500 times per hour (Olds 1956). Olds and his associates described the topographic organization of hypothalamic self-stimulation functions, employed self-stimulation of the brain as a screening method for tranquilizing drugs and demonstrated “positive reinforcement” produced by stimulating certain areas in the hypothalamus with iproniazid and other drugs (Olds, Killam and Bachy-Rita 1957; Olds and Olds 1958; Olds, Travis and Schwing 1960). 

            An operant behavioral method for studying self-maintained morphine addiction with implanted electrodes in the “pleasure” centers was first developed in 1961 by Weeks (Weeks 1961, 1962). Martin demonstrated in the 1960s that a “protracted abstinence syndrome” (PAS)  could be found six to nine months after stopping chronic opiate use in both humans and animals (Martin and Jasinski 1969). 

            This was the state of art in the biology of addiction research at the time neuropsychopharmacology was born.  




Ban TA. Conditioning and Psychiatry. Chicago; Aldine; 1964. p. 143-9. 

Ban TA. Conditioning and Psychiatry. London; Unwin; 196. p. 143-9. 

Delgado JMR, Roberts WW, Miller NE. Learning motivated by electrical stimulation of the brain.  Amer J Physiol 1954; 179; 587-93.  

Guthrie ER, Conditioning as a principle of learning. Psychol Rev 1930; 37: 412-28. 

Guthrie ER. Pavlov’s theory of conditioning. Psychol Rev 1934; 41: 199-208. 

Hilgard ER, Marquis DG. Conditioning and Learning. New York: Appleton-Century-Crofts; 1940. 

Hull CL A functional interpretation of the conditioned reflex. Psychol Rev 1929; 36: 498-511. 

Hull CL. Simple trial and error learning: a study in psychological theory. Psychol Rev 1930; 37: 241-56.  

Hull CL. Principles of Behavior. New York: Appleton-Century Croffts: 1943.  

Martin WR, Jasinski DR. Physiological parameters of morphine dependence in man - tolerance, early abstinence, protracted abstinence. Journal of Psychiatric Research 1969; 7: 9-17. 

Miller S, Konorski J. Sur une forme particuliè des reflexes conditionelles. CR Soc Bol 1928; 99: 


Olds J. Pleasure centers in the brain.  Sci Amer 1956; 193: 108-16. 

Olds J, Killam KF, Bachy-Rita F. Self-stimulation of the brain used as a screening method for tranquilizing drugs. Science; 1956; 124: 265-6. 

Olds J, Milner P. Positive reinforcement produced by electrical stimulation of septal area and other region of the brain. J Compr Physiol Psychol 1954; 419-27. 

Olds J, Olds ME. Positive reinforcement produced by stimulating hypothalamus with iproniazid and other compounds. Science 1958; 127: 1175-6. 

Olds J, Travis RP, Schwing RC.  Topographic organization of hypothalamic self-stimulating functions. J Comp Physiol Psychol 190; 53: 23-32. 

Schlossberg H. Conditioned responses in the white rat.  J genet Psychol 1934; 45: 303-35. 

Schlossberg H. Conditioned responses in the white rat. II.  Conditioned responses based upon shock  to the foreleg. J genet Psychol 1936; 49: 107-38. 

Schlossberg H. The relationship between success and the laws of conditioning. Psychol Rev 1937; 44: 379-94.  

Skinner BF. The concept of the reflex in the description of behavior. J gen Psychology 1931; 5: 27-58. 

Skinner BF. Conditioning and extinction and its relation to drive. J gen Psychology 1936; 14: 296-317. 

Skinner BF. The Behavior of the Organism. New York:  Appleton-Century-Crofts; 1938.  

Thorndike EL. Animal Intelligence. New York: Macmillan; 1911. 

Tolman EC.  Principles of Behavior in Animal and Man. New York: Appleton Century; 1932. 

Tolman EC.  Sign-Gestalt or conditioned reflex.   Psychol Rev 1936; 43: 366-85. 

Weeks JR. Self-maintained morphine addiction - a method for chronic programmed intravenous injection in unrestrained  rats. Federation Proceedings 1961; 20: 397-8. 

Weeks JR. Experimental morphine addiction: method for automatic intravenous injections  of unrestrained rats. Science 1962; 138: 143-4. 


February 7, 2019