The Tail of the Raccoon, Part II: Touching the Invisible – Scientific Commentary

 

Triggered Drug-Taking Due to Sign-Tracking
Arthur Tomie & Barbara Zito

I. Introduction

The Tail of the Raccoon, Part II: Touching the Invisible is the second story of The Sign Tracker Trilogy. The story depicts the role of Sign-Tracking in the drug addiction process. The purpose of the story is to improve the reader’s understanding of Sign-Tracking and how knowledge of Sign-Tracking can help to explain how voluntary, controlled drug use can, through repetition and ritual, transition into drug addiction.

II. The Science of Sign-Tracking
Sign-Tracking is a form of Pavlovian conditioning. Just as Pavlov’s dogs learned to salivate to the tone that signaled food, in Sign-Tracking procedures, the subject learns to act toward the object that signals food as though the object were actual food. That is, the Sign-Tracking subject will approach, contact, and “consume” the object. Keep in mind that the food is delivered regardless of what the subject does, so that Sign-Tracking does not serve the purpose of acquiring the food reward. Sign-Tracking is an acquired Pavlovian reflex that is triggered by the object without regard to the intention of the subject.

How can repetitions of voluntary casual drug use lead to the development of Sign-Tracking and the loss of self-control of drug-taking? Consider the following. Sign-Tracking develops due to object-reward pairings. Casual drug-taking typically involves using an object (cocktail glass, tooter, bong, etc) as a conduit to assist in consuming the drug (alcohol, cocaine, marijuana, etc). As a result of casual drug use, the object becomes a drug cue because the object is paired with the drug reward each time that the drug is consumed. This arrangement is depicted in the story when, each time Lepus takes the drug, he sees the vial just before getting high. These repetitions of casual, voluntary, intended drug-taking expose Lepus to still further repeated pairings of the vial with the potion. These conditions are conducive to the development of Sign-Tracking. The Sign-Tracking action sequence will lead to the ingestion of Alatro’s rewarding potion located inside the vial cue. This is a form of drug-taking that happens regardless of the intention of the subject. In this way, the development of Sign-Tracking leads to the loss of self-control of drug-taking.

With the discovery of Sign-Tracking, addiction scientists have uncovered a loss of self-control paradigm which models by analogy prominent features of drug addiction (Tomie, Brooks, and Zito, 1989; Tomie, 1995, 1996; Tomie, Badawy, and Rutyna, 2016; Flagel, Akil, & Robinson, 2009; Flagel, Watson, Robinson, & Akil, 2006). Features of Sign-Tracking that resemble drug addiction include the following: Sign-Tracking develops due to pairings of an object with a reward; object-reward pairings trigger the subject to perform the actions seen during drug-taking (approach, contact, and “consume” the object); Sign-Tracking is an acquired reflex, it is an involuntary response that is not subject to self-control. Sign-Tracking, therefore, is believed, in many cases, to be the root cause of the mysterious loss of self-control of drug-taking.

III. Triggered Drug-Taking Due to Sign-Tracking is Masked
The voices of addicts reveal another mysterious aspect of drug addiction. They say that they were blind-sided, that they were not aware that they were losing control over their drug-taking. In the words of addicts, “I never saw it coming” or “I was totally in shock when I realized I was trying to stop and couldn’t.” The words of addicts reveal that they cannot see their lack of self-control of their drug-taking. This is because drug-taking due to Sign-Tracking closely resembles voluntary drug-taking and, therefore, it is readily misconstrued as an intended act of drug-taking.

In the science lab, researchers have studied Sign-Tracking under conditions where voluntary, intended responding had previously been established. They found that Sign-Tracking responses were induced by cue-reward pairings and these Sign-Tracking responses so closely resembled voluntary responses that they were included in frequency counts of voluntary responses. The naked eye was unable to differentiate Sign-Tracking from voluntary responding. It was only through systematic manipulation of cue-reward arrangement that researchers were able to show that cue-reward pairings induced Sign-Tracking that looks like and is additive with voluntary responding (for reviews, see Hearst and Jenkins, 1974; Schwartz and Gamzu, 1977). The convergence of streams of Sign-Tracking responses with streams of voluntary responding results in elevated levels of responding that, prior to the discovery of Sign-Tracking, were mistaken for voluntary acts of reward-directed actions that were performed to excess (Tomie, Brooks, and Zito, 1989).

Sign-Tracking may be camouflaged so that it is mistaken for voluntary responding, and the conditions that produce this masking effect (voluntary responding directed at an object that is a reward cue) are precisely the same conditions that are employed in drug-taking (for detailed discussion, see Tomie, 1995 and 1996). The lesson of The Tail of the Raccoon, Part II: Touching the Invisible is that drug-taking due to Sign-Tracking is invisible because, it passes for voluntary drug-taking. Therein lays the conundrum for the drug abuser, who cannot understand, “Why can’t I quit?” The drug abuser can’t quit because the drug abuser cannot control Sign-Tracking. The action of drug-taking due to Sign-Tracking is disconnected from the intention of the drug abuser to quit. Because Sign-Tracking is invisible, “touching the invisible” describes the behavior of the drug abuser who is trying unsuccessfully to quit.

IV. Sign-Tracking Induced by Drug Reward
Scientists have provided numerous published reports showing that Sign-Tracking develops when an object is employed to signal the delivery of drug reward. For example, presenting a lever followed by an injection of cocaine induced rats to approach the lever and sniff the lever, even though the cocaine was delivered regardless of what the subject did (Uslaner, Acerbo, Jones, & Robinson, 2006). Other investigators have shown that presenting the lever as a cue for an infusion of cocaine will induce rats to approach the lever and press the lever, even though neither response was necessary to receive the injection of cocaine (Carroll & Lac, 1993; Carroll, Morgan, Lynch, Campbell, & Dess, 2002). Illumination of a light cue above a sipper tube filled with a cocaine solution provided rats with pairings of the light cue with cocaine’s rewarding effects, and induced rats to approach the location of the light cue (Di Ciano & Everitt, 2003; Falk & Lau, 1993, 1995), and the rats continued to approach the light cue even when placed at a distance from the cocaine sipper (Falk & Lau, 1993, 1995).
Carroll and Lac (1997) reported that pairing the insertion of a lever with an injection of amphetamine induced rats to press the lever, while other investigators have reported that pairing the insertion of a lever with an injection of heroin induced pressing of the lever (Lynch & Carroll, 1999; Roth, Casimir, & Carroll, 2002). Similar effects are observed with alcohol. Pairing the insertion of a lever with the presentation of a sipper tube filled with alcohol induced rats to press the lever, even though the alcohol sipper was delivered regardless of what the subject did (Tomie, Festa, Sparta, & Pohorecky, 1993). Pairing the brief illumination of a cue light with alcohol drinking induced approach to the location of the cue light (Falk, 1994; Falk & Lau, 1995; Krank, 2003; Krank, O’Neill, Squarey, & Jacob, 2008) and also resulted in elevated performance of an operant drug-seeking response required to obtain access to alcohol drinking (Krank, 2003; Krank, O’Neill, Squarey, & Jacob, 2008). Pairing the intermittent insertion and retraction of a sipper tube filled with alcohol induced elevated alcohol drinking from the sipper tube relative to controls receiving continuous access to the sipper tube filled with alcohol, indicating that the positive correlation between the sipper tube and the alcohol solution induced Sign-Tracking of alcohol drinking (Tomie, Miller, Dranoff, & Pohorecky, 2006; for review see Tomie & Sharma, 2014). Thus, addiction scientists have extensively documented that an object cue that is predictive of drug reward will induce cue-directed Sign-Tracking behavior, and in many of these cases, the performance of Sign-Tracking resulted in elevated drug-taking (Carroll & Lac, 1993, 1997; Carroll, Morgan, Lynch, Campbell, & Dess, 2002; Di Ciano & Everitt, 2003; Falk, 1994; Falk & Lau, 1993, 1995; Krank, 2003; Krank, O’Neill, Squarey, & Jacob, 2008; Lynch & Carroll, 1999; Roth, Casimir, & Carroll, 2002; Tomie, Festa, Sparta, & Pohorecky, 1993; Tomie, Miller, Dranoff, & Pohorecky, 2006; for review see Tomie & Sharma, 2013).

V. Sign-Tracking Induces Alcohol Drinking in Humans
The user is sitting in a tavern having a drink. Though he has had enough, he happens to look at the cocktail glass sitting in front of him. The mere act of looking at the cocktail glass triggers the user to Sign-Track. Without a thought, he picks up the cocktail glass and drinks from it. This is a triggered act of alcohol drinking, and will serve to prolong the ongoing alcohol drinking episode. This, in turn, will increase the likelihood of an episode of excessive alcohol drinking. The evidence (for review, see Tomie & Sharma, 2013) suggests that the poorly controlled alcohol drinking induced by Sign-Tracking leads to bouts of excessive alcohol drinking, and this contributes to elevated rates of problem drinking incidents (drunk driving, public intoxication, disorderly persons, assault, resisting arrest, domestic violence, etc).
Suppose your favorite drink is a double martini, extra dry, with two olives and an onion, served in a lead crystal highball glass. Suppose further that this is the only way that you drink … that all of the alcohol that you drink is consumed in this way. Under these conditions, your alcohol drinking repertoire is extremely narrow. While this does simplify the ordering of drinks (i.e., “I’ll have the usual”), the narrow drinking repertoire is an alcohol drinking style that is highly conducive to the development of Sign-Tracking. This is because alcohol’s rewarding effects are only experienced when the highball glass is present, making the highball glass an excellent cue that is highly predictive of alcohol reward. The highball glass will, therefore, readily elicit Sign-Tracking, resulting in reflexive acts of automatic and unintended alcohol drinking. Due to Sign-Tracking, therefore, the narrow drinking repertoire will be associated with binge episodes of excessive alcohol drinking and elevated rates of problem drinking.
Addiction nosologists studying the progression of alcoholism have confirmed the longitudinal trend toward the narrowing of the drinking repertoire (Jellinek, 1960; Cottler, Phelps, and Compton, 1995; McCreary, 2002), such that alcohol is eventually consumed only in the form of a favorite alcoholic beverage that is served only in a particular form of glassware. This style of alcohol drinking has been noted to presage the nosological progression into increasingly frequent episodes of excessive and poorly controlled alcohol drinking (Jellinek, 1960). The link between the narrowing of the drinking repertoire and the subsequent onset of problem drinking is consistent with the hypothesis that Sign-Tracking contributes to alcohol drinking in humans.
Additional evidence consistent with the Sign-Tracking hypothesis is provided by cultural anthropologists who noted higher rates of problem drinking in Northern Europe, as compared to Mediterranean Europe, even though the per capita consumption of alcohol in those regions are comparable (deLint, 1973; Heath, 1987). While there are many cultural aspects of alcohol drinking that may contribute to those regional disparities in problem drinking rates, it should be noted that the types of glassware used to consume alcoholic beverages differ across regions and in accordance with predictions of the Sign-Tracking hypothesis. North European cultures have widely adopted a style of alcohol drinking such that alcohol is consumed almost exclusively from specialized containers, included lead crystal stemware, goblets, and flutes, as well as metal ware in the form of beer mugs and ale steins.
This is in contrast to Mediterranean Europe, where alcohol is often consumed from common everyday glassware of the sort also used to consume water or other non-alcoholic beverages (Levin, 1990). When common everyday glassware is used to consume an alcoholic beverage, the common glassware is a poor alcohol cue because it is not highly predictive of alcohol reward. The common glassware, therefore, is unlikely to elicit Sign-Tracking, as compared to the specialized glassware that is used exclusively to consume alcoholic beverages. The specialized glassware is a far better cue because it is more highly predictive of alcohol reward. The link between specialized glassware and elevated rates of problem drinking is consistent with the hypothesis that Sign-Tracking contributes to alcohol drinking in humans.
These findings suggest that poorly controlled alcohol drinking in humans may be due to drinking styles related to the glassware used to consume alcoholic beverages. Several novel therapeutic remedies are suggested. For example, you could pour your favorite drink out of your favorite glassware and into a soup bowl or some other container that has never been used to drink an alcoholic beverage. Now that your favorite alcoholic beverage is sitting in the soup bowl, triggered alcohol drinking is far less likely to occur. This should reduce Sign-Tracking, so that the only alcohol that you will consume will be that which you intended. An additional therapeutic remedy suggested by the Sign-Tracking hypothesis is the following: convert the use of your favorite specialized alcohol glassware so that you use it only to drink non-alcoholic beverages. By using your favorite cocktail glass to drink milk, vegetable juice, chocolate drink, lemonade, water, iced tea, soda, etc, you will reduce the cue value of the cocktail glass as a signal for alcohol reward. This, in turn, will serve to reduce the likelihood going forward that your favorite cocktail glass will trigger Sign-Tracking.

VI. Sign-Trackers are Addiction Prone
The second story depicts differences between individuals in the tendency to exhibit Sign-Tracking behavior. The antics of the sons of Sign Tracker reveal that Lepus is more prone than Orion to develop Sign-Tracking. Though the brothers experience the same number of pairings of the rope with the syrup, Orion reacts to rope-syrup pairings in a sensible way, while Lepus reacts quite differently. Due to the pairings of the rope with the syrup, Orion learns that the presence of the rope signals the nearby availability of the syrup. Orion reacts to the information provided by the rope cue, by following the rope to the location of the storage pit. Lepus also learns that the rope is a signal for the nearby availability of the syrup, but reacts in an emotional way to the rope cue. Lepus becomes very excited by the sight of the rope. He is attracted to the rope. He runs to the rope, then licks and chews on the rope, treating the rope as though it were food. Eventually, and much to the dismay of Orion, Lepus becomes so obsessed with eating the rope that he rapidly chews right through it, sending the rope and the sweet treats to the bottom of the pit.

Though it’s the syrup that Lepus is after, his intention to get at the syrup is thwarted by his actions. This shows that his obsession with eating the rope, his performance of Sign-Tracking, is outside the realm of his control. Lepus is like his father. Lepus is a Sign Tracker. Thus, Lepus is unable to control himself when he is in the presence of the reward symbol.

Addiction scientists have discovered a close relationship between Sign-Tracking and drug addiction. They have found that the tendency of an individual to develop Sign-Tracking predicts the vulnerability of that individual to drug addiction (Flagel, Akil, & Robinson, 2009; Flagel, Watson, Robinson, & Akil, 2006; Tomie, Grimes, & Pohorecky, 2008). In the addiction science laboratory of Professor Terry Robinson and his associates at the University of Michigan Medical School, a large group of rats were assessed for their tendency to develop Sign-Tracking behaviors in response to the insertion of a lever paired with the delivery of food. Rats that more readily approached and contacted the lever were designated Sign Trackers (ST), while rats that react to the insertion of the lever by approaching the location of food delivery were designated Goal Trackers (GT). All rats are then tested for their tendency to self-administer an abused drug. Each rat was given the opportunity to perform a response that was required in order to receive an injection of an abused drug, such as cocaine, amphetamine, or morphine. ST rats, relative to GT rats, more rapidly acquire the drug-taking response (Beckmann, Marusich, Gipson, & Bardo, 2011), and ST rats, relative to GT rats, take the abused drugs more frequently (Saunders & Robinson, 2010, 2011), Moreover, ST rats, relative to GT rats, are more vulnerable to relapse to drug-taking following periods of drug abstinence (Saunders & Robinson, 2010, 2011; for review, see Meyer, Lovic, Saunders, et al., 2012). Thus, vulnerability to Sign-Tracking confers vulnerability to drug addiction.

Scientists are now asking the question, Why are ST rats more addiction-prone than GT rats?” One possible answer lies in the specifics of the experience encountered during the act of drug-taking. To obtain the rewarding effects of the drug, the subject is required to perform a voluntary or operant response, typically called the drug-taking response (sometimes called the drug-seeking response). The drug-taking response is almost invariably an action that is directed at a feature of the environment. Most typically the subject is required to make contact with an object. In doing so, the subject will experience the pairing of that object with the rewarding effects of the drug. As a result of extended training with the drug self-administration procedures, the ST rat, relative to the GT rat, will more likely develop Sign-Tracking directed at the object, resulting in contact with the object. Contacting the object is programmed to produce an injection of the abused drug. In other words, the specific actions of the drug-taking sequence in the drug self-administration laboratory provide experience that is conducive to the development of Sign-Tracking (Tomie, 1996). Note that this is very similar to the human experience, which the drug-self administration procedures are intended to model.

It should be noted that drug-taking procedures employed by humans are also conducive to the development of Sign-Tracking (Tomie, 1995). As noted earlier, humans typically employ an object as a conduit to aid in consuming the drug. Humans drink alcoholic beverages from a cocktail glass, snort cocaine through a coke tooter, and use a bong to smoke marijuana. Thus, drug-taking procedures employed by humans are also likely to lead those prone to Sign-Track into developing Sign-Tracking of drug-taking.

Those rats prone to develop Sign-Tracking also exhibit a constellation of other addiction-like behaviors. For example, ST rats tend to be more impulsive than GT rats, taking action quickly and without due consideration of the long term consequences (Lovic, Saunders, Yager, & Robinson, 2011; Tomie, Aguado, Pohorecky, & Benjamin, 1998). ST rats, like human drug addicts, tend to be risk-takers, prone to sensation-seeking and thrill-seeking. In addition, ST rats also tend to respond to novelty with arousal and excitement, rather than with caution (Beckmann, Marusich, Gipson, & Bardo, 2011), and this trait is also observed in humans prone to drug abuse. ST rats also exhibit physiological traits associated with vulnerability to drug abuse (Tomie, Aguado, Pohorecky, & Benjamin, 2000; Tomie, Tirado, Yu, & Pohorecky, 2004; for review, see Tomie, Grimes, & Pohorecky, 2008), as well as neurobiological markers differentially associated with drug addiction (Flagel, Watson, Robinson, & Akil, 2007). Therefore, addiction scientists have concluded that the tendency to perform Sign-Tracking behaviors may be the overt behavioral expression of a personality trait that confers vulnerability to drug addiction (Flagel, Akil, & Robinson, 2009).

GT rats are reward-centric. Their behavior is guided by their focus on the reward. Yet, GT rats are not addiction prone. ST rats, on the other hand, are signal-centric. Their behavior is not so much focused on the reward itself. Instead, their behavior is controlled by and focused on the signal associated with the reward. And, ST rats are addiction prone. It seems ironic that GT rats, even though they are more focused on the reward, are less prone to addiction, while ST rats even though they are less focused on the reward are more vulnerable to becoming addicted (for review, see Meyer, Lovic, Saunders, et al., 2012). This suggests that in certain cases drug addiction is more about the cues surrounding drug use than about the drug itself. Perhaps, the drug serves as the hook, but the cues form the barb of the hook that will not let go (Delmar, 2016). This much is clear. We are coming to understand that the attractiveness of the drug cue plays a major role in becoming hooked and in staying hooked (Flagel, Akil & Robinson, 2009; Robinson & Berridge, 1993, 2000; Tomie, Grimes, & Pohorecky, 2008; Tomie & Sharma, 2013).

VII. Sign-Tracking and the Neurobiology of Reward
The experience of a reward is accompanied by an emotional state, often described as a feeling of pleasure, satisfaction, well-being, or euphoria. Scientists have determined that the emotional feelings of euphoria or pleasure are related to activity in an area of the brain called the nucleus accumbens (NAC), which is often called the reward or pleasure center of the brain. The amount of activity in the NAC is determined by the levels of a brain chemical called dopamine. Higher levels of dopamine in the NAC are associated with stronger positive feelings of pleasure. For example, eating food induces the release of dopamine into the NAC, which leads to positive feelings of satisfaction and enjoyment.

Food, water, and sex are natural rewards. Each of these natural rewards produces an increase in DA levels in NAC that produces the positive emotional feelings of pleasure and euphoria. The elevated DA activity in NAC produces other effects as well. For example, any stimuli that happen to be present at the same time or immediately prior to the time that DA NAC activity is elevated by the natural reward are identified and associated with the positive emotional state produced by the natural reward. So, in addition to producing feelings of pleasure, DA activation of NAC also produces connections to stimuli (people, places, things, sounds, etc) that are present at the time of the euphoric episode. The elevated DA activity in NAC also produces an effect on motor responding called psychomotor activation. Thus, natural rewards induce elevated NAC dopamine, which, in turn produces three different types of effects: the emotional feelings of pleasure, the association of stimuli present during the experience of pleasure, and the motor responses of the psychomotor activation syndrome. It is the interplay among these three functions of the integrated reward system, each of which arises from the activation of the NAC, that form the major features of the rewarding experience.

The functional biological significance of the integrated reward system warrants further discussion. Consider the story of the starving beast. An ancient beast is on the verge of starvation. The famished beast picks up an oblong beige object, looks at it closely, then chews and swallows it. Fortunately, it’s an ear of corn, a food reward that activates the NAC. The reward system kicks into play, automatically giving rise to feelings of pleasure, accompanied by a pattern of motor activity called psychomotor activation. The beast just ate a piece of food, and psychomotor activation is the physical motor activity pattern that automatically follows, to organize the process of looking for more food. Psychomotor activation begins with a survey of the situation, an investigation of the environment, and a search for more food reward. To better survey the environment, the beast may stand erect, rearing and sniffing, looking around, visually scanning, and all the while evaluating the environment for food. But the food is lying on the ground, scattered among stones, dirt, twigs, and other non-food items. Because the ear of corn was the item that the beast looked at just before NAC activation, this oblong beige food object is highly likely to be associated by the NAC with strong feelings of pleasure. The association of the ear of corn with the emotional state of pleasure will improve the chances that the ear of corn will be selected as the target of the psychomotor activation syndrome. The beast locates on the ground nearby another small beige oblong object. It’s another ear of corn. Psychomotor activation automatically leads the beast to approach the ear of corn, pick up the ear of corn, and eat the ear of corn. After eating the second ear of corn, the beast feels another jolt of pleasure, which is experienced right after seeing the ear of corn, resulting in even more of an association between the corn and feelings of pleasure. In this way, each ear of corn becomes more tightly associated with pleasure, making the beast increasingly likely to approach, contact, and eat the corn.

Note that the beast is saved from starving by the integrated functions of the reward system (pleasure, association, psychomotor activation). Note also that for this beast, the process of directing eating responses at food was largely automatic, conferring on this individual beast more of a chance of surviving in a patchy world of scarce food resources. The beast survives, increasing the chances of reproductive success and will transmit this trait, the integrated reward system, to successive generations of progeny. Evolution has equipped the brain of modern beasts with the integrated reward system, deployed upon activation of NAC, to aid in survival. When we experience reward, we experience the emotion of pleasure, the association of the pleasure with stimuli present at that time, and the psychomotor activation pattern of responding.

Drugs of abuse, such as alcohol, cocaine, and opiates, all activate the same NAC reward system that is activated by natural rewards such as food, water, and sex, but the magnitude of the activation of the NAC by abused drugs may be many times greater than the effect produced by natural rewards. In this way, drugs of abuse hijack the reward system, diverting the system away from the sub-serving of survival, toward the sub-serving of addictive behavior.

How the integrated reward system sub-serves addictive behavior warrants further discussion. Consider the story of Johnny having a drink. Johnny is a moderate, social drinker. He enjoys having a few beers with his friends on the weekend. Lately, however, he has noticed that his beer intake has been gradually increasing, so that instead of having two beers at the poker game, he drinks four beers, or more. Drinking beer is pleasurable and mood-improving because the alcohol in the beer produces elevated DA activity in the NAC. In addition, activation of the NAC leads Johnny to associate other stimuli present at that time with these positive emotional feelings, so that Johnny feels good around his drinking pals. The NAC associates the people, places, and things that are present while drinking beer, with the positive feelings of beer-induced euphoria.

We should note that the stimulus that is most closely associated with the DA activation of the NAC is the beer bottle. This is because the beer bottle is seen in the moments in time just before the beer is consumed. The association between the beer bottle and the activation of DA in the NAC will cause the beer bottle to become the target of the psychomotor activation syndrome. This means that Johnny will notice the beer bottle. It conspicuously stands out. Johnny will also find that he is drawn toward the beer bottle. He will reach out and take the beer bottle in his hands, hold the beer bottle, and then drink from it. But the beer consumed due to the psychomotor activation syndrome is not the same as the beer that is consumed as a voluntary, controlled response. The psychomotor activation syndrome is a reflex coming out of the activation of the NAC. Psychomotor activation is not an intended action. Johnny did not decide to drink some more beer. Johnny is drinking beer on automatic pilot. In this way, the integrated reward system leads to beer drinking that occurs but was not intended or subject to self-control. Obviously, beer drinking beyond what is intended is outside the realm of free-will and will be difficult, if not impossible, to manage.

Due to alcohol’s effects on dopamine levels in NAC, alcohol use can occur even though you do not intend to have a drink. And, the more you drink, the more likely the psychomotor activation syndrome will produce unintended alcohol drinking. It is striking that the functions of the integrated reward system (pleasure, association, and psychomotor activation) bear a remarkable resemblance to the features of Sign-Tracking (for review, see Tomie, Grimes, & Pohorecky, 2008).

VIII. The Tail of the Raccoon, Part III: Departures
The Tail of the Raccoon, Part III: Departures, is the third story of The Sign Tracker Trilogy. In this story, Lepus is determined to quit Alatro’s potion and live with his family along the shores of the Great Lake, but he is not entirely free of memories of the potion’s pleasurable effects. Yet, by removing himself from the vicinity of Alatro’s den, and reminding himself of the depths of despair visited upon him by his obsession with the potion, Lepus makes good on his promise to remain drug-free. Until, that is, he is tempted by Alatro’s confederate, who offers Lepus a vial of the potion.

References:

Beckmann, J. S., Marusich, J. A., Gipson, C. D., & Bardo, M.T. (2011). Novelty seeking, incentive salience and acquisition of cocaine self-administration in the rat. Behavioural Brain Research, 216, 159-65.

Carroll, M. E., & Lac, S. T. (1993). Autoshaping i.v. cocaine self-administration in rats: effects of nondrug alternative reinforcers on acquisition. Psychopharmacology, 110, 5-12.

Carroll, M. E., & Lac, S. T. (1997). Acquisition of i.v. amphetamine and cocaine self-administration in rats as a function of dose. Psychopharmacology, 129, 206-14.

Carroll, M. E., Morgan, A. D., Lynch, W. J., Campbell, U. C., & Dess, N. K. (2002). Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences. Psychopharmacology, 161, 304-13.

Cottler, L. B., Phelps, D. L., & Compton, W. M., III. (1995). Narrowing of the drinking repertoire criterion: should it have been dropped from ICD-10? Journal of Studies of Alcohol, 56, 173-176.

deLint, J. (1973). The epidemiology of alcoholism: The exclusive nature of the problem, estimating the prevalence of excessive alcohol use and alcohol-related mortality, current trends and the issue of prevention. Toronto: Addiction Research Foundation of Ontario.

Delmar, M. (2016). Foreword. In The Tail of the Raccoon, Part III: Departures. Paperback, Createspace, 174 pages. Princeton, NJ: ZT Enterprises, LLC.

Di Ciano, P., & Everitt, B. J. (2003). Differential control over drug-seeking behavior by drug-associated conditioned reinforcers and discriminative stimuli predictive of drug availability. Behavioral Neuroscience, 117, 952-960.

Falk, J. L. (1994). The discriminative stimulus and its reputation: Role in the instigation of drug abuse. Experimental and Clinical Psychopharmacology, 2, 43-52.

Falk, J. L., & Lau, C. E. (1993). Oral cocaine as a reinforcer: acquisition conditions and importance of stimulus control. Behavioural Pharmacology, 4, 597-609.

Falk, J. L., & Lau, C. E. (1995). Stimulus control of addictive behavior: persistence in the presence and absence of a drug. Pharmacology, Biochemistry, and Behavior, 50, 71-5.

Flagel, S. B., Akil, H., & Robinson, T. E. (2009). Individual differences in the attribution of incentive salience to reward-related cues: Implications for addiction. Neuropharmacology, 56, 139-148.

Flagel, S. B., Watson, S. J., Robinson, T. E., & Akil, H. (2006). An animal model of individual differences in “conditionability”: relevance to psychopathology. Neuropsychopharmacology, 31, S262-S263.

Flagel, S. B., Watson, S. J., Robinson, T. E., & Akil, H. (2007). Individual differences in the propensity to approach signals vs goals promote different adaptation in the dopamine system of rats. Psychopharmacology, 191, 599-607.

Hearst, E., Jenkins, H. M. (1974). Sign-tracking: The stimulus-reinforcer relation and direted action. Austin, TX: Psychonomic Society.

Heath, D. B. (1987). Anthropology and alcohol studies: Current issues. Annual Review of Anthropology, 16, 99-120.

Jellinek, E. M. (1960). Alcoholism, a genus and some of its species. Canadian Medical Association Journal, 83, 1341-1345.

Krank, M. D. (2003). Pavlovian conditioning with ethanol: sign-tracking (autoshaping), conditioned incentive, and ethanol self-administration. Alcoholism: Clinical and Experimental Research, 27, 1592-1598.

Krank, M. D., O’Neill, S., Squarey, K., & Jacob, J. (2008). Goal- and signal-directed incentive: conditioned approach, seeking, and consumption established with unsweetened alcohol in rats. Psychopharmacology, 196, 397-405.

Levin, J. D. (1990). Alcoholism: A Biopsychosocial Approach. New York: Hemisphere Publishing Corp.

Lovic, V., Saunders, B.,T., Yager, L. M., & Robinson, T. E. (2011). Rats prone to attribute incentive salience to reward cues are also prone to impulsive action. Behavioural Brain Research, 223, 255-261.

Lynch, W. J., & Carroll, M. E. (1999). Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats. Psychopharmacology, 144, 77-82.

McCreary, D. R. (2002). Binge drinking in adulthood: the influence of gender, age, and beverage exclusivity. International Journal of Men’s Health, 1, 233-245.

Meyer, P. J., Lovic, V., Saunders, B. T., , et al. (2012). Quantifying individual variation in the propensity to attribute incentive salience to reward cues. PLoS One, 7, e38987.

Robinson, T. E., & Berridge, K. C. (1993). The neural basis of drug craving: An incentie sensitization theory of addiction. Brain Research Reviews, 18, 247-291.

Robinson, T. E., & Berridge, K. C. (2000). The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction, 95 (Suppl.), S91-117.

Roth, M. E., Casimir, A. G., & Carroll, M. E. (2002). Influence of estrogen in the acquisition of intravenously self-administered heroin in female rats. Pharmacology, Biochemistry, and Behavior, 72, 313-318.

Saunders, B. T., & Robinson, T. E. (2010). A cocaine cue acts as an incentive stimulus in some but not others: implications for addiction. Biological Psychiatry, 67, 730-736.

Saunders, B. T., & Robinson, T. E. (2011). Individual variation in the motivational properties of cocaine. Neuropsychopharmacology, 34, 1668-1676.

Schwartz, B., & Gamzu, E. (1977). Pavlovian control of operant behavior: An analysis of autoshaping and its implications for operant conditioning (pp. 53-97). In: Honig, W. K., Staddon, J. E. R., Eds. Handbook of operant behavior. Englewood Cliffs, NJ: Prentice-Hall.

Tomie, A. (1995). CAM: An animal learning model of excessive and compulsive implement-assisted drug-taking in humans. Clinical Psychology Reviews, 15, 145-167.

Tomie, A. (1996). Locating reward cue at response manipulandum (CAM) induces symptoms of drug abuse. Neuroscience & Biobehavioral Reviews, 20, 505-535.

Tomie, A., Aguado, A. S., Pohorecky, L. A., & Benjamin, D. (1998). Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping. Psychopharmacology, 139, 376-382.

Tomie, A., Aguado, A. S., Pohorecky, L. A., & Benjamin, D. (2000). Individual differences in pavlovian autoshaping of lever pressing in rats predict stress-induced corticosterone release and mesolimbic levels of monoamines. Pharmacology, Biochemistry, and Behavior, 65, 509-517.

Tomie, A., Badawy, N., Rutyna, J. (2016). Sign-Tracking Model of Loss of Self-Control of Drug-Taking. In: Recent Advances in Substance Abuse. Open access e-book. Avid Science: Berlin. Published April 2016.

Tomie. A., Brooks, W., & Zito, B. (1989). Sign-tracking: The search for reward. In S. Klein, S. and R. Mowrer (Eds.), Contemporary Learning Theories: Pavlovian Conditioning and the Status of Traditional Learning Theory, pp. 191-223. Lawrence Erlbaum Associates, Hillsdale, NJ.

Tomie, A., Festa, E. D., Sparta, D. R., & Pohorecky, L. A. (2003). Lever conditioned stimulus-directed autoshaping induced by saccharin-ethanol unconditioned stimulus solution: effects of ethanol concentration and trial spacing. Alcohol, 30, 35-44.

Tomie, A., Grimes, K. L., & Pohorecky, L.A. (2008). Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse. Brain Research Reviews, 58, 121-135.

Tomie, A., Miller, W. C., Dranoff, E., & Pohorecky, L. A. (2006). Intermittent presentations of ethanol sipper tube induce ethanol drinking in rats. Alcohol and Alcoholism, 41, 225-230.

Tomie, A., & Sharma, N. (2013). Pavlovian Sign-Tracking Model of alcohol abuse. Current Drug Abuse Reviews, 6, 201-219.

Tomie, A., Tirado, A. D., Yu, L., & Pohorecky, L. A. (2004). Pavlovian autoshaping procedures increase plasma corticosterone and levels of norepinephrine and serotonin in prefrontal cortex in rats. Behavioural Brain Research, 153, 97-105.

Uslaner, J. M., Acerbo, M. J., Jones, S. A., & Robinson, T. E. (2006). The attribution of incentive salience to a stimulus that signals an intravenous injection of cocaine. Behavioural Brain Research, 169, 320-324.

Zito, B., & Tomie, A. (2014). The Tail of the Raccoon: Secrets of Addiction. Paperback, Createspace, 70 pages. Princeton, NJ: ZT Enterprises, LLC.

 

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