A considerable body of clinical and laboratory data suggest that behavioral factors, including both classical and operant conditioning, play an important role in the development and maintenance of drug dependence. This discussion will focus on some of the major contributions of behavioral research in this area as illustrated by the papers we have just heard. Since much of this work has been carried out in opiate users, I will, for the sake of clarity and consistency, focus on this particular area, bearing in mind the potential application of these findings to other forms of substance abuse.

 

CONDITIONED RESPONDING IN OPIATE USERS

The role of conditioning factors in opiate dependence and withdrawal has been explored by a number of research groups (Wikler, 1968; O'Brien, 1981) including our own (Meyer, 1979). In the course of such studies it has been noted that under certain circumstances, addicts will respond to the mere anticipation of drug effects or to an injection of saline as if they had actually received an opiate drug. In our own studies (Meyer, 1979) addicts pretreated with a narcotic antagonist like naltrexone will exhibit such responses (ie, constricted pupils, diminished respirations, feelings of euphoria) when exposed to subsequent injections of "blocked" heroin. O'Brien's group has made similar observations, as illustrated by the data presented here today (O'Brien, 1981).

 

The role of such conditioned responses in the perpetuation of drug dependence has been the subject of considerable speculation. Our own observation has been that individuals who manifest conditioned opioid-like responses to injections of "blocked" heroin also report relatively high levels of drug craving, even after conditioned responding to blocked heroin is no longer evident. Consistent with this observation they also tend to relapse more readily when discharged into the community, suggesting that conditioned responding to drug-related stimuli may be a poor prognostic sign in this population.

 

Another important finding of behavioral research in the addictions is the observation by Wikler (1968) that rats previously addicted to morphine will exhibit "wet dog shakes", a sign of morphine abstinence, when placed in an environment in which they had previously experienced morphine addiction and withdrawal. Similarly, in individuals with a history of opiate dependence such conditioned abstinence responses may be elicited by stimuli previously associated with opiate intoxication or withdrawal. For example, ex-addicts and patients on methadone will exhibit conditioned abstinence symptoms when shown pictures of other addicts "shooting up", drug paraphrenalia, etc. These symptoms are indistinguishable from those produced by narcotic withdrawal (O'Brien, 1974).

 

The observation of conditioned abstinence phenomena in both animals and man has led to speculation about the role of such responses in the genesis of relapse. In our own experience (Mirin, 1974) conditioned abstinence phenomena are characteristically accompanied by increased drug craving and drug seeking behavior. Where such behavior culminates in the experience of drug related (ie, pharmacologic) reinforcement a powerful link has been forged in the behavioral chain leading to relapse. In this context Wikler (1973) has postulated that effective blockade of opiate reinforcement should result in the eventual extinction of opiate using behavior. Though clearly applicable to animal models of addiction (Carnathan, 1977) this process has yet to be demonstrated in man.

 

A number of laboratories have attempted to test the extinction hypothesis under controlled conditions. In an earlier study by O'Brien and associates (1974), addicts pre-treated with the narcotic antagonist cyclazocine were allowed to self-administer hydromorphone (Dilaudid) or saline under double-blind conditions. Initially, injection of either substance was followed by subjective reports of euphoria. In most subjects, this conditioned response quickly extinguished; in a few, however, conditioned responding to "blocked" injections of hydromorphone was maintained. In our own studies (Meyer, 1979), ex-addicts pretreated with naltrexone were allowed to self-administer increasing doses of intravenous heroin. About half discontinued opiate use after three or four unsuccessful attempts at "getting high." In these subjects the decision to discontinue heroin challenges of antagonist blockade seemed more consistent with a process of cognitive labeling (ie, that heroin was really "unavailable") than extinction in the classical sense.

 

A second group of naltrexone-treated individuals persisted in self-administering heroin (R = 15 trials) despite antagonist blockade of opiate effects. Interestingly, it was this group that manifested conditioned autonomic responses (ie, pupillary constriction, diminished respiratory rate) and euphoria after injecting "blocked" heroin. Compared to those subjects who stopped challenging antagonist blockade after only a few trials, they also reported relatively high levels of drug craving, even after heroin was no longer available to them.

 

The practical implication of those findings were subsequently explored in our follow up studies (Meyer, 1979) where we found that in the month after discharge the rate of relapse to heroin use was much higher among those who manifested conditioned autonomic responses to blocked heroin. Thus, one might reasonably speculate that in the course of maintaining an addiction some addicts develop a particular responsiveness to conditioned stimuli which signal increased drug availability. These stimuli, in turn, trigger a rise in drug craving and drug seeking behavior. On the research ward this propensity is manifested by prolonged challenging of antagonist blockade. In the community it is expressed by a high rate of drop out from antagonist treatment and subsequent relapse to heroin use.

 

SCHEDULE EFFECTS ON DRUG USING BEHAVIOR

 

A relatively neglected area of behavioral research involves the role of schedule effects in the development and maintenance of drug taking behavior. The work of both Dews (1981) and Stollerman (1981) suggests that, at least in animals, drug seeking behavior may be profoundly influenced by factors specific to the relationship between the behavior itself and the delivery (ie, schedule) of reinforcement. Our own, albeit less rigorous, observations (Meyer, 1979) suggest that scheduling may also effect drug seeking behavior in man. For example, addicts working for heroin made available on a fixed interval (FI) schedule will perform such work in a pattern reminiscent of Fl responding in animal studies. Work output (in this case, lever pulling) characteristically increased just prior to the "purchase" of each heroin dose. Moreover, this pattern of responding was maintained whether subjects waited two, four, or six hours between each injection (Meyer, 1979).

In contrast, addicts "on the street" usually experience opiate reinforcement on an uncertain (ie, variable interval) schedule. The effect of this schedule on operant responding (ie, hustling behavior) is to assure that such behavior is more or less continuous, declining only in the immediate post injection period.

 

Finally, lest we adhere too closely to a behavioral focus, Dr. Mule's (1981) paper reminds us that, in man, drug seeking behavior is also shaped by the psychosocial and biological context in which it occurs. Indeed, even the consumption of a powerful reinforcer like heroin is influenced by the drug-using behavior of one's peers. Thus, in our subjects who were allowed to get high on heroin, the frequency of drug self-administration (ie, q2h, q4h or q6h) for each individual was clearly influenced by the drug using behavior of their intoxicated peers.

 

To summarize, behavioral studies of the type presented here today have shed considerable light on a very complex area. Though at first glance drug-using behavior appears to be under conscious control, it is subtly, but clearly, shaped by behavioral contingencies. Opiate addiction, like the other so-called "volitional" disorders, develops in the context of a series of voluntary choices. Once a repetitive pattern of drug use is established, however, this behavior is clearly shaped by a host of other factors, including conditioned responding, schedule effects, and factors particular to the psychosocial milieu in which drug consumption and reinforcement takes place. It is these commonalities which link the various addictive disorders and make them so difficult to treat. Hopefully, the insights provided by behavioral research will provide a foundation upon which effective treatment strategies may be based.

 

REFERENCES

 

Carnathan G, Meyer RE and Cochin J: Narcotic blockade, length of addiction and persistence of intravenous morphine self-administration in rats. Psychopharmacology 54:67-71, 1977

Dews PB: Maintenance of behavior by "schedules": An unfamiliar contributor to the maintenance of the abuse. Presented at a Symposium of the International Anti-Drug Abuse Foundation, April 1981

Meyer RE and Mirin SM: Operant analysis. In: RE Meyer and SM Mirin (eds.), The Heroin Stimulus. New York: Plenum Press, pp 61-91, 1979

Meyer RE, Mirin SM and Zackon F: Community outcome on narcotic antagonists. In: RE Meyer and SM Mirin (eds.), The Heroin Stimulus. New York: Plenum Press, pp 215-230, 1979

Mirin, SM: A multimodality approach to opiate addiction. Psych Opin 11:35-42, 1974 Mule SJ: Behavior in excess: An examination of the volitional disorders. Presented at a

Symposium of the International Anti-Drug Abuse Foundation, April 1981 O'Brien CP: The effects of conditioning on human opiate addicts. Presented at a

Symposium of the International Anti-Drug Abuse Foundation, April 1981 O'Brien CP, Chaddock B, Woody G and Greenstein R: Systematic extinction of

addiction associated rituals using narcotic antagonists. Presented in part at the

American Psychosomatic Society Annual Meeting, March 1974

Stolerman IP: Behavioral analysis of drug taking and drug dependence. Presented at a

Symposium of the International Anti-Drug Abuse Foundation, April 1981 Wikler A: Dynamics of drug dependence: Implications of a conditioning theory for

research and treatment. Arch Gen Psychiatry 28:611-616, 1973

Wikler A: Interaction of physical dependence and conditioning. A Res New and Mental

Disorders Proc 46:280-287, 1968