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.     

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.     

A Primer of Covert Sensitization

Covert sensitization is the first of a family of behavior therapy procedures called covert conditioning initially developed by Joseph Cautela in the 1960s and 1970s. The covert conditioning procedures involve the use of visualized imagery and are designed to work according to operant conditioning principles. When working with cooperative clients to treat maladaptive approach behaviors, covert sensitization has been found to be a humane and effective alternative to in vivo aversion therapy procedures that employ aversive stimuli such as chemicals and electric shock. This primer describes covert sensitization, provides examples and notes representative research. Guidelines for use and suggestions for further readings are also included.     

Chemical aversion conditioning as a treatment for alcoholism: A re-analysis

The literature on chemical aversion conditioning is characterized by the lack of controlled clinical research. The existing data derive primarily from methodologically inadequate studies. Although short-term conditioned aversion reactions to alcohol have been demonstrated, the independent efficacy of this technique in clinical treatment remains to be shown. Beyond the failure to demonstrate the value of adding chemical aversion conditioning to more standard treatments for alcoholism, evaluation in terms of broader outcome criteria (e.g. safety, intrusiveness, acceptability, the availability of alternative methods, and cost-effectiveness) indicates that chemical aversion conditioning cannot be recommended as a standard form of treatment for alcoholism.     

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.     

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.     

Ontogenetic changes in the modulation of taste aversion learning by home environmental cues in rats

Eight experiments using 611 rats as subjects were conducted to define and analyze an age-related phenomenon of conditioned taste aversion. When consumption of sucrose solution was followed by LiCl-induced illness in the animals' home, acquisition of the aversion to sucrose solution was retarded in preweanling (18-day-old) rats. This effect was not found in adults or in slightly older (21-day-old) rats. Place of testing had no effect in the younger two age-groups, but in adults manifestation of the acquired aversion was retarded when they were tested in the home. There was no interaction between place of conditioning and testing for any age. The locus of the environmental influence on conditioning in preweanling rats was found to be the place of tasting rather than place of illness, retention interval, or testing. Also, the effect was found to be invariant under minor variations in familiarization of the animal with the non-home environment. The principle emerging from these data and others is that the home environment can have a significant influence on learning and conditioning in the immature rat.     

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.     

Age-dependent facilitation of taste-footshock conditioning by prior exposure to the training context

Among adult rats, gustatory stimuli are easily associated with illness, but not with external unconditioned stimuli such as footshock. Recent evidence indicates, however, that this cue-to-consequence specificity may vary ontongenetically. The present studies examined the acquisition of an aversion to a taste paired with footshock in 5- and 15-day-old rats. Consistent with previous reports, 5-day-old rats avoided the taste that preceded footshock, while 15-day-old subjects did not express an aversion to the taste paired with footshock. Exposure to the training context for either 1 or 5 h prior to conditioning disrupted taste-footshock conditioning in the 5-day-old subjects. For the 15-day-old subjects, 1 h of pre-conditioning exposure to the training context had no effect on conditioning, whereas a longer duration of preexposure promoted conditioning to the taste cue. The results suggest ontogenetic differences in stimulus selection.     

Augmentation of taste conditioning by a preconditioned odor.

Five experiments explored facilitated taste-aversion conditioning (odor-mediated taste augmentation), using rats that experienced odor (A) and taste (X) in an A+/AX+ design. Augmentation occurred when the stimuli were presented simultaneously during AX+ conditioning, and significantly weaker conditioning occurred after a sequential presentation (Experiment 1). Experiments 2 and 3 demonstrated that augmented conditioning decreased if the odor aversion was reduced through preexposure or extinction following A+ conditioning. A second-order conditioning explanation was not supported by the results of Experiment 4. Experiment 5 showed that extinction of the odor aversion after AX+ conditioning did not alter the strength of the augmented taste aversion. Odor-mediated taste augmentation is similar to potentiation, in which odor and taste cues operate in a synergistic, not competitive, manner.     

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.     

Effects of Cerebroventricle Administration of Acidic Fibroblast Growth Factor on Conditioned Taste Aversion Learning in Rats

Wistar strain rats were given acidic fibroblast growth factor (aFGF) or denatured aFGF into their cerebroventricle before taste aversion conditioning for saccharin solution. Animals administrated with aFGF showed significantly lower aversion threshold for saccharin at the 1st day and preference ratios for saccharin vs distilled water at the 4th, 6th, and 7th day after the conditioning than those administered with denatured aFGF. These results suggests that aFGF in the cerebrospinal fluid facilitates acquisition of the conditioned taste aversion learning.     

Differential Acquisition of Aversion by Two Distinctive Contexts Paired with Lithium-Induced Illness

In three experiments using rats as subjects, we investigated the role of the hedonic properties of the CS in context aversion conditioning. In Experiment 1, rats were allowed to drink water in two different contexts, L-S (Light room and Small cage) and D-B (Dark room and Big cage). Rats' consumption of water was higher in the D-B than in the L-S context. This result was taken as evidence for the L-S context eliciting a state of uneasiness that interferes with drinking plain water. In Experiments 2 and 3, rats were injected with lithium after placement in the L-S or the D-B context. In a blocking test (Symonds & Hall, 1997), the L-S context showed conditioning since it blocked the acquisition of aversion by a novel taste, quinine (Experiment 2) or salt (Experiment 3). By contrast, the D-B context failed to show conditioning, that is, no blocking was observed with salt or quinine. These results suggest that the hedonic properties of the context used as the CS may affect its acquisition of associative strength when paired with an internal aversive stimulus.     

Element preexposure, neophobia, and conditioned aversion to a compound flavor stimulus

Preexposure to one or two elements of a compound flavor stimulus greatly reduced a neophobic reaction to the compound but did not attenuate conditioned flavor aversion in rats. Results indicated that (1) a preexposure effect on conditioned aversion to a flavor compound is not likely to be obtained if subjects initially show a strong neophobic reaction to the elements and (2) the level of neophobia at the time of conditioning has little influence on conditioned flavor aversion.     

Higher-order conditioning and sensory preconditioning of a taste aversion with an exteroceptive CS1

An exteroceptive stimulus compound (context) was employed as CS₁ in higherorder conditioning (H-OC, Experiments I and II), and sensory preconditioning (SPC, Experiment III) of a saccharin (CS₂) aversion in rats. The results indicated that aversions were established with the H-OC as well as with the SPC procedures. Stimulus generalization and first-order conditioning explanations were ruled out by appropriate controls. A CS₁-extinction period, performed prior to testing, did not affect the H-OC aversion, whereas it reduced the SPC aversion at least partially. These findings imply that interoceptive (taste, nausea) and exteroceptive stimuli (context) are readily associable in rats. Implications of the resemblance between the SPC procedure and long-delay taste-aversion learning are discussed.     

Perceptual learning in flavor aversion: evidence for learned changes in stimulus effectiveness

Rats were exposed to the compound flavors AX and BX, presented in alternation, and to CX on a separate block of trials. Generalization to BX after aversion conditioning with AX was less than to CX. An equivalent effect was found when the nature of the common element was changed after preexposure but not when the common element was omitted during preexposure, during conditioning and test, or both. Rats conditioned with X alone again showed less aversion to BX than to CX; similarly, rats conditioned with a novel flavor (Y) showed less aversion to BY than to CY. These effects support the proposal that intermixed preexposure to AX and BX enhances the perceptual effectiveness of their unique features, A and B.     

Augmentation, not blocking, in an A+/AX+ flavor-conditioning procedure

An A+/AX+ Pavlovian conditioning design typically produces weakened or blocked conditioning to stimulus X. Two experiments were conducted in which rats first received an odor (A+) paired with an emetic US, and then received odor and taste (AX+) paired with the US. In both experiments, the preconditioned odorfacilitated conditioning to the taste. In Experiment 1, a group that received two odor-illness pairings in A+ conditioning had a stronger taste aversion than a group that only had a single odor-illness pairing. Experiment 2 demonstrated that the strengthened taste aversion in the A+/AX+ condition was not due to stimulus generalization. The results represent a unique outcome in the flavor-aversion literature that is similar to potentiation. We propose that this facilitated conditioning to X in the A+/AX+ design be termedaugmentation.     

Conditioned taste aversion is enhanced when the unconditioned stimulus is presented in a different context

Using a conditioned taste aversion procedure with rats as the subjects, two experiments examined the effect of presenting a conditioned stimulus (CS saccharin solution) in one context followed by an unconditioned stimulus (US LiCl) in a different context. Experiment 1 showed that animals which received the above-mentioned procedure (Group D) showed a more marked conditioned aversion to the CS than animals which were given both the CS and the US in the same context (Group S). Experiment 2 found that in both Group D and Group S, aversion to the CS increased when the subjects were exposed to the conditioned context after the conditioning. These findings supported the argument that the strength of the CS-US association acquired during conditioning is compared with that of the context-US to determine the magnitude of aversion revealed to the CS.     

Intermittent reinforcement in behaviour therapy

It is suggested that intermittent reinforcement may be of value in retarding the tendency towards relapse in aversion therapy. An experiment with rats was conducted to examine the effects of intermittent shocks in approach-avoidance conflict learning. Intermittent reinforcement was shown to produce marked resistance to extinction in this type of avoidance learning. In a field-investigation of conditioning treatment of enuresis, intermittent reinforcement was found not to retard acquisition unduly and to give promise of reducing the relapse rate. A longer follow-up period is required to permit a final evaluation of the procedure.