Wednesday, 28.10.2020

Peter R. Martin: Historical Vocabulary of Addiction

Conditioning

 

         As noted in the current electronic version of Oxford English Dictionary (OED), the noun conditioningis a combination of the verb condition and the suffix ing, whose function is to render the verb into a noun of action.  The word condition has been in use since the 14th century as either a noun or verb; as a noun, the word originates from Middle English and Old French condicion derived from the Latin condiciōn-em (in later times, commonly spelt conditiōn-em) which means “a compact, stipulation, agreement upon terms.”  As a verb, it originates from the Old French condicionne-r, corresponding to medieval Latin conditiōnāre, meaning “to impose a condition on, to limit with conditions.”  The meaning that is the subject of the current discussion is most appropriately linked to the verb: “To teach or accustom (a person or animal) to adopt certain habits, attitudes, standards, etc.; to establish a conditioned reflex or response in.”  Thus, conditioning is defined in OED as: “The training or accustoming of a person or animal to give conditioned responses.”  Ban (2008) described conditioning as: “referring to the learning of some particular response.  The conditional stimulus is one that was originally ineffective but that, after being paired with an unconditional stimulus, evokes the conditional response.” 

         First mention in the English language with the relevant meaning of the verb condition, according to OED, is attributed to reports (Yerkes and Morgulis 1909) of methods in animal psychology involving the canine salivary response operationalized by the Russian physiologist Ivan Petrovich Pavlov and his collaborators from the period of 1899-1909: “Pawlow's Method... Separate components of a complex sound which conditions a ‘fundamental’ reflex, will produce reflexes (the so-called partial reflexes) at a certain relative intensity.” This methodology from Pavlov’s laboratory consisted of eliciting the canine salivary reflex in response to diverse sensory stimuli (that typically would not produce salivation) by repeatedly pairing the stimulus in question with one that naturally serves to activate the salivary reflex.  This is referred to as Pavlovian, classical or respondent conditioning.  The verb condition has subsequently become part of common parlance, widely used in philosophy and literature (Ewing 1944): “During its first twelve months the child acquires many habits and may be conditioned in various ways, for instance in regard to cleanliness. But unless this conditioning is brought into relation with the dynamic structure of focused impulse which develops in the second year, it will wear out or break down.”

         The noun conditioning was first use in the English language, according to OED, in the context of conditioned emotional reactions in infancy: “Steps taken to condition emotional responses... The infant…was tested with his blocks immediately afterwards to see if they shared in the process of conditioning (Watson and Rayner 1920).”  The authors proposed linkage of emotional reaction patterns to stimuli within the child’s environment as the mechanism whereby the much wider range and complexity of adult emotions develop through the process of conditioning—an example of developmental transformation via conditioning of the Lockean tabula rasa of earliest childhood.  The noun conditioning has subsequently become widely accepted in literature (Huxley 1932):  “All conditioning aims at that: making people like their unescapable social destiny.” 

         Skinner (1937) introduced the term operant as a descriptor of conditioning: “There is also a kind of response which occurs spontaneously in the absence of any stimulation with which it may be specifically correlated... I shall call such a unit an operant and the behavior in general, operant behavior.”  Additionally, Kimble and Hilgard (1940) used the term instrumental to denote operant conditioning: “When the occurrence of the reinforcement is contingent upon the organism's behavior the procedure may be termed instrumental conditioning.”  In operant/instrumental conditioning, behaviors are shaped by the presentation of reward after a desired behavior occurs spontaneously, and the learning is strengthened with each subsequent associated presentation of the reward with spontaneous occurrences of the desired behavior. 

         Extinction of a conditioned response, regardless of whether it is classical or operant, occurs when it is no longer rewarded or punished.  As a result, diminution, or fading of the non-reinforced conditioned response is observed over time.

         As learning forms the mechanistic underpinnings (“the currency”) of addiction (Kalant, LeBlanc and Gibbins 1971; Stolerman 1992; Martin, Lovinger and Breese 1995), conditioning provides an heuristic framework for understanding and experimentally modelling components of the disorder (Wikler 1973).  Operant conditioning seems most relevant in pathogenesis of primary drug use disorders, wherein initially rewarding effects of the drug of abuse precede progression to out-of-control use despite negative consequences (White 1989; Volkow and Morales 2015).  On the other hand, in drug use disorder secondary to underlying other psychopathology, the notion of reinforcement of classical conditioning seems more appropriate (White 1989).  For example, in psychiatric disorders in which contextual (situational) conditioned fear responses underpin psychopathologic manifestations (Sotres-Bayon, Bush and LeDoux 2004; Tamminga 2006), self-administration of drugs of abuse can modify neurotransmission in relevant regions of the amygdala/hippocampus/prefrontal cortex so as to diminish the intensity of disturbing psychic symptoms; with repeated self-medication to cope with painful psychological symptoms, individuals may eventually develop out-of-control drug use or addiction. 

         Treatment of addiction can be understood as extinction of conditioned response(s) that contribute to pathological use of alcohol/drugs resulting in diminution/cessation of use through various pharmacopsychosocial interventions (Martin ,Weinberg and Bealer 2007).  Analysis of self-destructive, out-of-control self-administration of drugs of abuse that characterizes addiction reveals multiple component behaviors, each of which are potentially subject to the principles of conditioning and extinction, e.g. drug-seeking behavior, effects of intoxication and withdrawal (Tatum, Seevers and Collins 1929; Wikler 1973; O’Brien 1975) and, in particular, various elements of tolerance (Kalant, LeBlanc and Gibbins 1971).  Neuroadaptation to repeated drug use is now recognized to involve allostatic change (Koob 2017) in addition to classical constructs of tolerance and dependence (Kalant, LeBlanc and Gibbins 1971), which do not allow the organism to return to its original behavioral state (prior to first drug use) with respect to response(s) to the drug of abuse, and therefore, are not strictly amenable to the principles of extinction.  In fact, clinical observation suggests that the earlier in life alcohol/drug use begins and the longer the  associated conditioning has persisted within the behavioral repertoire, the more severe and difficult to treat is the disorder: “anyone — normal, neurotic or psychopathic, manic depressive or schizoid — can become an alcoholic addict if he drinks long enough and heavily enough (on the average about a decade), and that the younger he is when he starts his drinking, the less likelihood there is for his successful treatment in a mental hospital” (Fleming and Tillotson 1939). 

         Applying the principles of classical conditioning to treatment of alcohol use disorder was first described in Russia and pursued subsequently in the United States (Thimann 1943).  Voegtlin (1940) implemented a method whereby: “the nauseant drugs, emetine and apomorphine, were used to elicit the unconditioned reflex of nausea and vomiting, and the sight, smell, and taste of alcoholic beverages served as the conditioned stimulus.”  Thereafter, an analogous strategy of linking alcohol use with a distressing state via pharmacotherapy was employed in patients with alcohol use disorder (Hald and Jacobsen 1948): “The organism is sensitised to alcohol after intake of tetraethylthiuramdisulphide…(disulfiram, or Antabuse).  Alcohol given to persons previously treated with this otherwise innocuous substance produces dilatation of the facial vessels, increased pulmonary ventilation, raised pulse-rate, and general uneasiness. The symptoms appear to be the result of an increased formation of acetaldehyde from alcohol.”  So as not to re-experience these very unpleasant symptoms of the alcohol/disulfiram reaction, the patient elects not to drink, ideally progressing in time to extinction of drinking behavior (Martensen-Larsen 1948).

         Behavioral pharmacology provides a strategy based on learning theory to determine the capacity of drugs of abuse to modify behavior in a test organism (e.g., behaving rodents among others, nonhuman primates or even humans) using the paradigm of self-administration (Schuster and Thompson 1969) and substitution to suppress withdrawal and determine cross-tolerance or cross-dependence (Kalant, LeBlanc and Gibbins 1971).  In the self-administration paradigm, the fundamental task is to quantify the effort that an experimental animal will expend to receive the drug in question via various routes of administration and determine interventions that might modify the rewarding value of drugs.  By comparisons of behavioral responses elicited by the test drug with those of other agents that have well-defined pharmacological actions, the test drug’s relative ability to reinforce self-administration and the neuropharmacological mechanisms underpinning these responses may be elucidated (Schuster and Thompson 1969).  This paradigm may equivalently be employed to determine the capacity of a well-characterized drug to substitute for or treat withdrawal from the test agent.  In addition, one can determine if a drug being tested for treatment of addiction to the drug in question may favorably alter the pattern or degree of its self-administration. 

         Attempts to better understand the fundamental neurobiology of conditioning has led to experiments in much less complex organisms to unravel phenomena involved in learning (Castellucci, Pinsker, Kupfermann and Kandel 1970) with, as yet, unclear reductionistic implications for conditioning as a model of addiction.  In addition, other constructs than classical or operant conditioning have been invoked in expanding the role of drives in behaviors that are not readily understandable in terms of survival of the species, which may gain more relevance as one tries to understand what addictive behaviors have wrought in our society (Knoll 2003).

 

References:

Ban TA. Conditioning Behavior and Psychiatry. New Brunswick, N.J.: Aldine Transaction; 2008.

Castellucci V, Pinsker H, Kupfermann I, Kandel ER. Neuronal Mechanisms of Habituation and Dishabituation of the Gill-Withdrawal Reflex in Aplysia. Science. 1970;167(3926):1745.

Ewing AC. Evolutionary Ethics. By J. S. Huxley. (Oxford University Press, 1943. Pp. 84. Price 2s. net.). Philosophy. 1944;19(73):170-1.

Fleming R, Tillotson KJ. Further Studies on the Personality and Sociological Factors in the Prognosis and Treatment of Chronic Alcoholism. N Engl J Med. 1939;221(19):741-5.

Hald J, Jacobsen E. A drug sensitising the organism to ethyl alcohol. The Lancet. 1948;252(6539):1001-4.

Huxley A. Brave new world. 1st ed. after the printing of two hundred and fifty de luxe copies. Garden City, N.Y: Doubleday, Doran & Co.; 1932.

Kalant H, LeBlanc AE, Gibbins RJ. Tolerance to, and dependence on, some non-opiate psychotropic drugs. Pharmacol Rev. 1971;23(3):135.

Kimble GA, Hilgard ER (Ernest R. Hilgard and Marquis’ Conditioning and learning. New York, NY: Appleton-Century Company; 1940.

Knoll J. Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives. Neurochem Res. 2003;28(8):1275-97.

Koob GF. The Dark Side of Addiction: The Horsley Gantt to Joseph Brady Connection. J Nerv Ment Dis. 2017;205(4):270-2.

Martensen-Larsen O. Treatment of alcoholism with a sensitising drug. The Lancet. 1948;252(6539):1004-5.

Martin P, Lovinger D, Breese G. Alcohol and other abused substances. In: Munson P, Mueller R, Breese G, editors. Princ Pharmacol Basic Concepts Clin Appl. New York: Chapman & Hall; 1995. p. 417-52.

Martin PR, Weinberg BA, Bealer BK. Healing Addiction: An Integrated Pharmacopsychosocial Approach to Treatment. Hoboken, New Jersey: John Wiley & Sons, Inc.; 2007.

O’Brien CP. Experimental Analysis of Conditioning Factors in Human Narcotic Addiction. Pharmacol Rev. 1975;27(4):533.

Schuster CR, Thompson T. Self administration of and behavioral dependence on drugs. Annu Rev Pharmacol. 1969;9(1):483-502.

Skinner BF. Two Types of Conditioned Reflex: A Reply to Konorski and Miller. J Gen Psychol. 1937;16(1):272-9.

Sotres-Bayon F, Bush DEA, LeDoux JE. Emotional Perseveration: An Update on Prefrontal-Amygdala Interactions in Fear Extinction. Learn Mem. 2004;11(5):525-35.

Stolerman I. Drugs of abuse: behavioural principles, methods and terms. Trends Pharmacol Sci.  1992;13:170-6.

Tamminga CA. The Anatomy of Fear Extinction. Am J Psychiatry. 2006;163(6):961.

Tatum AL, Seevers MH, Collins KH. Morphine addiction and its physiological interpretation based on experimental evidences. J Pharmacol Exp Ther. 1929;36(3):447.

Thimann J. The Conditioned Reflex as a Treatment for Abnormal Drinking: Its Principle, Technic and Success. N Engl J Med. 1943;228(11):333-5.

Voegtlin WL. The treatment of alcoholism by establishing a conditioned reflex. Am J Med Sci. 1940;199:802-9.

Volkow ND, Morales M. The Brain on Drugs: From Reward to Addiction. Cell. 2015;162(4):712-25.

Watson JB, Rayner R. Conditioned emotional reactions. J Exp Psychol. 1920;3(1):1-14.

White NM. Reward or reinforcement: What’s the difference? Neural Basis Reward Reinf Conf Honour Peter M Milner. 1989;13(2):181-6.

Wikler A. Dynamics of Drug Dependence: Implications of a Conditioning Theory for Research and Treatment. JAMA Psychiatry. 1973;28(5):611-6.

Yerkes RM, Morgulis S. The method of Pawlow in animal psychology. Psychol Bull. 1909;6(8):257-73.

 

December 26, 2019