An appraisal of chemical aversion (emetic therapy) approaches to alcoholism treatment.

More than 35,000 alcoholics have received chemical aversion (emetic therapy) in at least 75 settings worldwide since the 1930s. This consummatory aversion (CA) treatment, which pairs ethanol ingestion with emetically induced nausea, incorporates the highly efficient variety of learning known as taste aversion (TA) conditioning. The CA literature indicates that emetic therapy should induce conditioned alcohol aversions in many alcoholics. Such aversions have been widely reported by clinicians and have been confirmed by recent psychophysiological evidence. Long standing evidence of treatment effectiveness is found in the results of private hospitals which have consistently produced 1-yr abstinence rates approximating 60%. Diminished alcohol craving is a frequently reported benefit. Few experimental evaluations have been completed, as is generally the case for all alcoholism treatments, but those which used methodologically sound temporal parameters during conditioning have supported the clinical efficacy of emetic therapy. The clear need for more definitive research notwithstanding, there are compelling indications that emetic therapy is a useful component of multimodal treatment within certain alcoholic populations. However, its availability is severely limited. Many alcoholics could probably benefit from expanded treatment availability. The time is ripe for a reevaluation of resistances to the clinical use of emetic therapy alcoholism treatment.     

Forgetting, preconditioning CS familiarization and taste aversion learning: An animal experiment with implications for alcoholism treatment

The rapid taste aversion acquisition, which typically occurs in many species when ingestion of a novel flavor precedes gastrointestinal distress, is retarded by preconditioning familiarity with the CS flavor. This CS familiarity effect (CSFE) might contraindicate taste aversion approaches to alcoholism treatment since alcoholics are quite accustomed to the tastes of alcoholic beverages. However, many alcoholics do develop strong nausea—induced alcohol aversions under appropriate conditioning parameters. Additionally, the CSFE is attenuated in rats by repeated conditioning trials including discrimination training. The present animal experiment was conducted to determine if the CSFE could additionally be weakened by process of forgetting, i.e. by preconditioning withdrawal of a familiar flavor analogous to an alcoholic's ‘drying out’ before psychotherapeutic intervention. Using saccharin as the CS flavor and cyclophosphamide as the conditioning agent, Sprague-Dawley derived rats acquired no aversions when conditioning was attempted immediately after flavor familiarization. However, significant and equivalent saccharin aversions were observed when conditioning was delayed for either 20 or 100 days after familiarization. These findings imply that the efficiency and cost effectiveness of taste aversion approaches to alcoholism treatment might be enhanced by a pretreatment period of abstinence from alcohol ingestion.     

Taste-aversion retention: An animal experiment with implications for consummatory-aversion alcoholism treatments

Inquiries into the longevity of illness-induced aversions (TAs) in animals are relevant to consummatory-aversion (CA) treatments of human alcoholism. The range of nausea reactions that accompanied the relapses of some alcoholics who had acquired alcohol aversions during covertsensitization (verbal aversion) alcoholism treatment has implicated CA forgetting as one probable contributor to recidivism. CA forgetting is operationalized as aversion diminution during postconditioning periods in which Ss abstain from contact with the target substance. TAs of varying strengths were induced in groups of Sprague-Dawley rats that received low, medium or high doses of the illness-inducing drug cyclophosphamide following saccharin-solution ingestion. TA retention was assessed following saccharin-free intervals of 2–40 days. Each Ss' retention interval was followed by 30 days of two-bottle preference testing, thereby additionally permitting an assessment of TA extinction following differing degrees of TA forgetting. Low-dose Ss displayed moderate strength TAs that were forgotten within 20 days and that had little resistance to extinction when testing began shortly after conditioning. Medium-dose Ss displayed stronger TAs having greater resistance to both forgetting and extinction. Unlike these low- and medium-dose TAs, high-dose TAs were impervious to aversion degradation as a result of forgetting. This finding is interpreted as supporting the attempted induction of intense nausea during covert-sensitization and chemical aversion (emetic therapy) alcoholism treatment. Other related conditioning procedures that may contribute to effective treatment are also discussed.     

Chemical aversion treatment of alcoholism: Lithium as the aversive agent

Animal work indicating flavour aversion produced by chemical aversion therapy (CAT) with lithium might be effective in the treatment of alcoholism led to this treatment being given to 25 patients. The abstinence rate six months later of 36% was significantly better than the 12% rate for an equivalent group of patients, treated with a disulfuram-like drinking deterrent, calcium carbimide. The rate for the CAT group improves to 47% if 8 patients are excluded who did not develop sickness reactions to lithium. CAT with lithium appears safe given proper medical precautions.     

Chemical aversion conditioning in the treatment of alcoholism: further comments.

The literature on consummatory aversion (CA) conditioning in rats does provide a well-developed theoretical foundation for chemical aversion conditioning. Nevertheless, differences between rats and humans in CA learning suggest caution in extrapolating from the animal laboratory to the treatment of alcoholic patients. Serious methodological problems with studies of emetic therapy with alcoholics preclude unambiguous evaluation of its effects. Emetic therapy is an intrusive and relatively costly form of treatment which has not been shown to be more effective than alternative, less costly methods. The onus is on proponents of this method to demonstrate its specific advantages over alternative treatments.     

Methods for assessment of aversion treatment in fetishism with masochism

An operant conditioning measure is described, which showed that faradic shocks were aversive in a patient whose fetishism was associated with masochism. The patient's response was in keeping with expectations drawn from the initial measures, since faradic aversion produced rapid improvement of the masochism with subsequent improvement of the fetishism, and increased enjoyment of normal sexual relations. The operant conditioning and semantic differential measures accurately reflected clinical changes after treatment, and are useful to assess progress. Masochism does not necessarily contra-indicate aversion treatment.     

Further evidence for the summation of latent inhibition and overshadowing in rats’ conditioned taste aversion

Repeated exposures to a target taste (X) attenuated subsequent development of rats’ conditioned aversion to X (latent inhibition effect). Presentation of another taste (A) after X in conditioning (serial X-A compound conditioning) also attenuated conditioned X aversion compared with conditioning without A (overshadowing). Furthermore, the latent inhibition and overshadowing effects summed to show the least conditioned aversion in the rats given both the target preexposures and the serial X-A compound conditioning treatment. These results question the validity of the comparator hypothesis as an explanation for Pavlovian conditioning of rats’ conditioned taste aversion.     

Taste preconditioning augments odor-aversion learning

On the basis of previous work that has shown a taste can potentiate odor-aversion conditioning in AX+ conditioning, 6 experiments used rats to examine the effects of pairing a preconditioned taste (A) with a novel odor cue (X) in an A+/AX+ aversion conditioning design. Experiments 1A and 1B demonstrated that a preconditioned taste produced a robust odor aversion that was significantly stronger than a potentiated odor aversion. The results of Experiment 2 showed that the robust odor aversion produced by A+/AX+ conditioning was not the result of the potentiated odor aversion summating with generalization from the taste aversion. The augmented odor aversion was produced only when the taste and odor stimuli were presented simultaneously (Experiment 3) and the preconditioned taste aversion was intact at compound conditioning (Experiment 4). Pairing a novel odor with a preconditioned taste was not sufficient to condition an aversion to odor (Experiment 5), although other results implicated a role for an association between odor and taste in the odor augmentation effect (Experiment 6). The present results have implications for current models of taste + odor interactions in flavor-aversion conditioning.     

Exteroceptive context in tasteaversion conditioning and extinction: odour, cage, and bottle stimuli

Five experiments investigated the extent to which the exteroceptive context, present on a saccharin aversion conditioning trial with rats, controlled the resulting aversion on one-bottle extinction tests and subsequent preference tests. The presence or absence of the specific odour which had been present on the conditioning trial was found not to influence saccharin intake on extinction tests, whereas the presence of the particular compartment in which, and the bottle from which, the saccharin had been consumed greatly suppressed saccharin intake as compared to the absence of these elements. Preference tests, performed in the respective conditioning contexts, showed extinction to be specific to the compartment + bottle context: groups that had extinguished their saccharin aversion in a context different from the conditioning context, retained their aversion in the conditioning context. No such specificity was found for the odour context. However, in the absence of the taste stimulus during the extinction phase, the odour that had been present on the conditioning trial did control the amount of water consumed, whereas the compartment+bottle context did not. Moreover, on preference tests, groups that had consumed water during extinction in the presence of the odour context, evidenced a lesser saccharin aversion than groups not exposed to the odour. The results are interpreted as demonstrating that rats learn about taste, odour, cage and bottle stimuli on a taste-aversion conditioning trial, and that taste and bottle stimuli seem to be the most salient.     

Taste aversions conditioned by the aversiveness of insulin and formalin: role of CS specificity

Experimenters in the past have reported that when insulin is used as the unconditioned stimulus (US), rats will learn an aversion to a sodium chloride but not a sucrose solution, whereas with formalin as the US, they will learn an aversion to a sucrose but not a saline solution. The present experiments failed to confirm these findings. Aversions to sucrose were conditioned with insulin and aversions to sodium chloride were conditioned with formalin. The use of a more concentrated sucrose solution in the present study may have been responsible for the successful sucrose-aversion conditioning with insulin. Although the source of the discrepancy in findings concerning aversion conditioning with formalin remains unclear, experiments ruled out numerous possibilities. These experiments also showed that sodium chloride aversion conditioning with formalin is a highly robust phenomenon that occurs with a variety of conditioned stimulus durations and formalin doses, with distributed and massed training, in male and female rats, and even if saline is not the only novel solution presented during conditioning. Furthermore, the aversion can be detected with both single-stimulus and choice test procedures.     

Drugs employed in the treatment of alcoholism: rat data suggest they are unnecessarily severe

A tacit assumption, which has often been made by practitioners of both chemical aversion therapy (CAT) and deterrent therapy of alcoholism, is that efficacy of a drug depends mainly on how noxious it is. We conducted two experiments which challenge this assumption. These experiments compared five noxious drugs employed in the treatment of alcoholism, with lithium, in regard to their ability to reduce rats' drinking of a familiar, readily consumed, ethanol (10% v/v) solution. In both experiments, the dose of lithium was equivalent, in terms of body weight, to the largest daily recommended human dose: the dose of each of the five, noxious drugs was twice this equivalent. In the first experiment, the CAT drugs emetine, ipecac and succinylcholine were compared with lithium: in the second, the deterrent therapy drugs citrated calcium carbimide and disulfiram were compared. Despite the use of comparatively smaller doses of lithium, none of the noxious drugs administered in either experiment produced stronger ethanol aversions than lithium. This supports the use of lithium in CAT, and suggests that unnecessarily noxious drugs are being used in the treatment of alcoholism.     

The relative contributions of predictiveness and salience in flavor aversion learning

Two experiments investigated the relative influence of cue predictiveness and stimulus salience on flavor aversion learning. In the first study experimental subjects experienced a nonsalient strawberry flavor and a different, more salient flavor prior to illness on each of the first three conditioning trials; the nonsalient strawberry and salient lemon were paired with illness on the fourth trial. This treatment resulted in a strong aversion to the strawberry flavor and on aversion to the lemon flavor. In contrast, animals which had experienced only a single pairing of strawberry, lemon, and illness acquired a strong aversion to lemon and no aversion to strawberry, while animals which had experienced only the pairing of different flavors and illness on each of the first three trials developed a strong aversion to both strawberry and lemon. Experiment 2 replicated the results of the experimental condition of the first study but also included a “blocking” condition in which subjects received three strawberry and illness pairings prior to a strawberry-lemon-illness pairing. Subjects in the blocking condition developed only a weak aversion to strawberry, and this aversion did not block the development of a strong lemon aversion. Apparently, in order for a nonsalient flavor cue to block the acquisition of an aversion to a more salient cue, the nonsalient flavor must not only be paired with illness but also be more predictive of illness than the more salient flavors also paired with illness. The data were discussed in terms of the R. A. Rescorla and A. R. Wagner's associative model (1972, in Classical conditioning II: Current research and theory, New York: Appleton-Century-Crofts), R. A. Rescorla's catalytic model (1982, Journal of Experimental Psychology: Animal Behavior Processes,8, 131–141), and N. J. Mackintosh's attentional model (1975, Psychological Review,82, 276–298) of conditioning.     

Second-order conditioning during a compound extinction treatment

Two conditioned taste aversion experiments with rats were conducted to establish if a target taste that had received a prior pairing with illness could be subject to second-order conditioning during extinction treatment in compound with a flavor that also received prior conditioning. In these experiments, the occurrence of second-order conditioning was indicated by protection from extinction of the aversion elicited by the target taste. This possibility, although intuitive, deserves attention because current associative models [e.g., Rescorla, R. A., & Wagner, A. R. (1972). A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and nonreinforcement. In A. H. Black & W. F. Prokasy (Eds.), Classical conditioning II: Current research and theory (pp. 64-99). New York: Appleton-Century-Crofts.] predict exactly the opposite outcome, namely, that compound extinction of two CSs should result in enhanced extinction.     

Human classical aversion conditioning: Nausea versus electric shock in the reduction of target beverage consumption

Two experiments were conducted to investigate the effectiveness of the nausea-pro-ducing Pseudo-Coriolis Effect (PCE) in conditioning aversions to beverage consumption. The first experiment assessed the effectiveness of this procedure while controlling for demand characteristics. The second experiment compared this procedure with electrical aversion conditioning. This study demonstrates the effectiveness and relative superiority of the PCE in classical aversion conditioning. Consideration is given to the parameters and potential applications of this procedure     

Taste-mediated potentiation of noningestional stimuli in rats

Holtzman rats drank saccharin in a distinctive environmental chamber prior to lithium-induced toxicosis. This treatment was administered four times. These animals subsequently drank less water or familiar saline in the chamber than animals which received water in the environment during conditioning. In addition, these environmental stimuli blocked the formation of a lithium-mediated coffee aversion more if they were conditioned in the presence of saccharin than if they were conditioned in the presence of water. Such differential blocking provided further evidence that the presence of a taste during conditioning facilitated aversion learning to the environmental chamber.     

Formation of food aversions in cancer patients receiving repeated infusions of chemotherapy

Patients receiving emetogenic chemotherapy for cancer have been found to develop aversions to normal dietary items consumed in close temporal relation to treatment administrations. These aversions are presumed to develop via conditioning processes as demonstrated in experimental studies of food aversion learning. The present study used a prospective, longitudinal design to evaluate the possible role of conditioning in the formation of aversions to normal dietary items in women receiving adjuvant chemotherapy for breast cancer. Patients were monitored for the development of aversions to foods and beverages consumed in the 24 hr periods before and after each of eight consecutive chemotherapy infusions beginning with the initial infusion. Data on the prevalence, course, and prediction of aversions to normal dietary items are reported. These results pointed to similarities and differences between aversions formed to normal dietary items during chemotherapy treatment and aversions formed to taste stimuli during experimental conditioning studies. In addition to their theoretical significance, results also suggest possible strategies for preventing the clinical problem of aversions to normal dietary items in chemotherapy patients.     

Flavor aversions produced by contingent drug injection: Relative effectiveness of apomorphine, emetine, and lithium

Shortly after rats began drinking saccharin solution, different groups of them were injected with different doses of apomorphine, emetine, or lithium. A control group was not injected at all. Six days later, the rats were given free access to saccharin solution and to water. Aversions to saccharin solution were obtained in all injected groups and tended to become more pronounced as the dose level increased. At similar dose levels, lithium produced the most pronounced aversions, apomorphine produced the weakest aversions, and emetine was intermediate. A follow-up study with squirrel monkeys confirmed that lithium produces more pronounced aversions than either emetine or apomorphine. From these results, it seems worthwhile to try lithium in the chemical aversion treatment of alcoholism.     

Flavour-odour compound conditioning: Odour-potentiation and flavour-attenuation

Five experiments employed a toxiphobia conditioning paradigm to examine the strengths of odour and flavour aversions when conditioned separately and in compound. When conditioned in compound, odour aversions were stronger than when conditioned separately, i.e., the flavour potentiated the odour (Experiment Ia), but flavour aversions were weaker than when conditioned separately, i.e., the odour attenuated the flavour (Experiment Ib). The duration of exposure to the reinforced compound governed the nature of the interaction between the components: at a brief exposure, the flavour overshadowed the odour; at a long exposure, the flavour potentiated the odour (Experiment II). The remaining experiments examined the mechanism subserving the potentiation effect. Experiment III demonstrated that extinction of the flavour associate of the odour attenuated the odour aversion but further conditioning of the flavour did not strengthen the odour aversion. Experiment IV confirmed this effect of extinction but also found a comparable attenuation of the odour aversion from extinction of a separately conditioned flavour. Experiment V examined the previous failure to influence the strength of the odour aversion by strengthening the flavour aversion. In this experiment, conditioning the flavour associate or a separately conditioned flavour with a more potent US augmented the strength of the odour aversion. The results did not provide support for the idea that the potentiation phenomenon reflects the formation of within-compound associations but did indicate that a potentiated odour aversion could be modulated by manipulations designed to alter the US representation.     

Forgetting of recently acquired or recently reactivated memories

Four experiments compared the rates of forgetting following acquisition of a conditioned aversion and following a reactivation treatment given long after conditioning had been completed. The “reactivation treatment” consisted of a single presentation of the unconditioned stimulus, a procedure known to reinstate, following substantial forgetting, the behavior seen immediately after conditioning. It was first determined that the decrement in performance 1, 3, or 7 days later tended to be more rapid just after original conditioning than following a reactivation treatment given 27 days after conditioning. Subsequent experiments confirmed that the forgetting seen 3 or 7 days after original conditioning was in fact greater than forgetting 3 or 7 days after the reactivation treatment that had followed conditioning by 27 days; also, tests permitted rejection of the hypothesis that this effect could be attributed to nonassociative (systemic) consequences of the conditioning situation. Finally, tests indicated that retention 24 hr after a reactivation treatment was significantly better if the reactivation treatment followed conditioning by 27 days than if it were given just 3 min or 24 hr after conditioning. The central observation emerging from this study, that forgetting is more rapid following original learning than following a temporally remote reactivation treatment, was discussed in terms of potential interactions between the age (or accessibility) of a memory and processes that might be instigated by a reactivation treatment.