Incentive-sensitization Theory Of Addiction Research Articles

A Proof of Concept Study to Assess the Imbalance of Self-Reported Wanting and Liking as a Predictor of Problematic Addictive Behaviors

AbstractTolerance, one of the key features of addiction, is a highly debated criterion for behaviors, considered controversial and difficult to assess. The Incentive-Sensitization Theory of Addiction (IST) provides a robust empirical background on the dynamics of the motivational and hedonic systems underlying addiction, reflecting tolerance. The aim of this proof-of-concept study was to introduce wanting and liking as an IST-based measure of tolerance. Survey data were analyzed on two potentially problematic substance use behaviors (alcohol and nicotine use) and seven potentially problematic behaviors (eating, gaming, pornography use, social media use, internet use, television series watching, and working) of 774 participants (517 women, Mage = 35.8 years, SD = 11.84), using linear regression models. The models describing the relationship between usage frequency and the difference between self-reported wanting and liking were significant for all of the investigated substance use and potential behavioral addictions. As a general pattern, the balance of wanting and liking was disrupted with increasing usage/behavior frequency, with a steady increment in wanting in all investigated cases. The findings indicate that the proposed approach holds promise as an empirically robust tool for addiction research, offering the potential to compare substance and behavioral addictions on a unified dimension.

Hedonic Overeating–Questionnaire: Exploring interactive effects between wanting, liking, and dyscontrol on body mass index

The Hedonic Overeating–Questionnaire is a brief self-report measure for the trait assessment of liking (pleasure to eat; consummatory reward component), wanting (food craving; anticipatory reward component), and dyscontrol (loss of control over eating). In the original validation study, higher scores on each of the three subscales related to higher body mass index (BMI). However, theories on food reward and self-regulation suggest that overeating and obesity may also result from interactions between these aspects. Therefore, we reanalyzed the data of the original, cross-sectional study (N = 2504, 53% female) and explored whether liking, wanting, and dyscontrol scores interactively predicted BMI. Indeed, there was a significant interaction effect Wanting × Dyscontrol on BMI such that higher dyscontrol scores related to higher BMI, particularly at high wanting scores. The other two-way interactions and the three-way interaction were not significant. Results do not support certain theories on food reward (e.g., the incentive-sensitization theory of addiction and its application to obesity), which would suggest an interactive effect between liking and wanting on BMI. However, they do support dual systems models of self-regulation that suggest that overeating and obesity result from an interplay of strong bottom-up impulses (here: wanting) and weak top-down control (here: dyscontrol).

A mechanistic staging model of reward processing alterations in individuals with binge-type eating disorders.

Altered reward processing is thought to characterize binge-type eating disorders, but the exact nature of these alterations is unclear. A more fine-grained understanding of whether specific aspects of reward processing contribute to the development or maintenance of binge eating may point to new therapeutic targets and personalized treatments. The incentive sensitization theory of addiction proposes that repeated use of a substance increases the desire to approach a reward ('wanting') but not pleasure when consuming the reward ('liking'), suggesting that reward processes driving addiction change over time. We hypothesize that the same may be true for binge eating. Further, consistent with the maladaptive scaling hypothesis, reward processing may be heightened for multiple reinforcers in at-risk individuals but become tuned toward food once binge eating is initiated. In this article, we propose a mechanistic staging model of reward processing in binge-type eating disorders that synthesizes existing data and posits that alterations of reward processing depend on illness stage and reward type. We outline translational methods for testing key hypotheses and discuss clinical implications. Considering reward processing alterations in relation to illness stage has the potential to improve treatment outcomes by ensuring that the mechanisms targeted are personalized to the individual patient. PUBLIC SIGNIFICANCE: Individuals with binge-type eating disorders experience alterations in their desire for, and pleasure from, food. We believe that the exact nature of these alterations in reward processing change over the course of illness-from the at-risk state to an established illness. If true, treatments for binge-type eating disorders that target reward processing should be personalized to the illness stage of the patient.

RF12 | PSUN103 Wireless Mobile Device Overuse and Obesity: Understanding the Neuroscience, Implications and Interventions

Abstract Background While wireless mobile device (WMD) overuse might be perceived as normal behavior in people of all ages, the pathophysiology of WMD addiction is similar to that of substance addiction. Increasing prevalence of disorders related to screentime/sedentary lifestyle such as obesity, dyslipidemia, prediabetes, and type 2 diabetes mellitus calls for comprehensive and cost-effective interventions. Objectives We aimed to synthesize existing data on the neuroscience that underlies WMD addiction, its adverse health outcomes and suggest practical strategies to achieve life-technology balance at home and work. Methods Comprehensive search of databases (PubMed and MEDLINE) was conducted until May 2021, for smartphone, screentime and phone addiction. The data were collected as part of a population-based educational initiative, Phreedom (Freedom from smartPhone), to inspire individuals to achieve life-technology balance. Results From the initial 655 citations, 234 were included. The addictive use of WMDs was linked to the 'incentive sensitization theory of addiction': repeated exposure to potentially addictive stimuli (i.e., notifications) can cause persistent structural and functional brain changes in the prefrontal cortex. As a result, an individual's executive functions and cue-reactivity could be impaired. The hyper-reactive dopamine system could also drive this compulsive behavior in the form of a habit-loop of cue, craving, response, and reward. Each hour/day increase in screentime was associated with 0.05-0.07 increase in body mass index (BMI) (p < 0.001), likely due to food marketing, distracted eating, reduced satiety, and procrastination of physical activity. Overuse of WMDs was associated with insufficient and low-quality sleep, daytime tiredness, daytime sleepiness, depression, and daily cognitive failures. Nine of 10 Americans reported using a technological device in the hour before bed. The more interactive the device, the higher the difficulty falling asleep and unrefreshing sleep (p < 0.05). The younger the age at initial exposure and the longer the duration of exposure, the higher the odds of adverse health outcomes, such as illegal substance use. High users of screens were more likely to have been diagnosed with anxiety or depression, requiring medication. Practical strategies to disrupt the addictive dopamine habit-loop included WMD triage and uncluttering, eliminating redundant notifications, deleting time-consuming applications, modifying the digital environment at home and work, and replacing screentime with greentime. Other tactics could include using an alarm clock, wearing a wristwatch, specifying times to check emails and social media, refocusing teams to decrease reliance on text messages and lowering expectations of immediate responses. Conclusions While it would be irrational to suggest complete avoidance of all WMDs, moderation, balance, and real-life engagement together with strategies aimed at disrupting the dopamine habit loop will be critical components of any intervention plan. Educating patients about the neuroscience of WMD addiction and empowering them with tips to curb WMD use might impact their behavior substantially. Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement.

SUMMARYAlthough midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTADA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTADA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNSTGABA→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTADA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.

The most 100 cited papers in addiction research on cannabis, heroin, cocaine and psychostimulants. A bibliometric cross-sectional analysis

The number of citations a peer-reviewed article receives is often used as a measure of its importance and scientific impact. This paper identifies, describes and categorizes the highly cited papers in addiction research on cannabis, heroin, cocaine and psychostimulants. Highly cited papers were identified in the Web of Science Core Collection database. Several bibliometric indicators were calculated. Social network analysis was applied to draw groups of authors and institutions with the greatest number of collaborations and co-words. The number of citations for the top 100 cited articles ranged from 649 to 4,672. The articles were published in 40 journals. The subject category Substance Abuse included 10 papers. The United States was the most productive country (79 papers), followed by the United Kingdom (9). The main funding institutions were the National Institutes of Health in the United States. The network of collaboration between authors distributes the 352 researchers into 53 groups. The three most cited works address the neural basis of drug craving as an incentive-sensitization theory of addiction, the clinical and research uses of the Addiction Severity Index, and the neurocircuitry of addiction. Scientific literature on addictions is widely dispersed both in multidisciplinary and specific journals of neurology, psychiatry and addictions, with relatively few publications providing most of the citations. An ongoing challenge for this field is the concentration of highly cited papers coming from a select number of countries, with the United States being the research hub of the world, with the highest volume of publications and total citations.

Sign tracking predicts cue-induced but not drug-primed reinstatement to methamphetamine seeking in rats: Effects of oxytocin treatment.

The incentive sensitisation theory of addiction posits that drug-associated stimuli become imbued with incentive motivational properties, driving pathological drug seeking. However, pre-existing variability in the incentive salience to non-drug reward cues ('sign trackers' (STs); 'goal trackers' (GTs)) is also predictive of the desire for and relapse to cocaine and opioids. Here, we asked whether variation in propensity to attribute incentive salience to a food cue is predictive of reinstatement to the highly addictive psychostimulant methamphetamine (METH), and whether treatment with the promising anti-addiction therapy oxytocin differentially reduces METH behaviour between STs and GTs. Rats were trained to associate a Pavlovian cue with delivery of a sucrose pellet over 8 days. They then received jugular vein catheters for intravenous METH self-administration, followed by behavioural extinction, and cue-induced and METH-primed reinstatement to METH-seeking behaviours. Oxytocin was administered prior to self-administration and reinstatement tests. Despite the self-administration of similar amounts of METH, STs reinstated more to METH cues than did GTs, yet METH-priming reinstated STs and GTs similarly. Furthermore, oxytocin attenuated cue-induced reinstatement more so in STs than in GTs, and reduced METH-primed reinstatement to a greater extent in the top quartile of reinstaters, indicating that oxytocin treatment may be most effective for those at highest risk of addiction. This pre-existing bias towards reward cues presents a possible tool to screen for METH addiction susceptibility and may be useful for understanding the neurobiology of addiction and for pharmacotherapeutic discovery.

What Drives Work Addicts to Action? The Extended Model of Work Craving

The theory of work craving highlights three pathological components of work addiction: the behavioral wanting component (an obsessive-compulsive desire for work), the hedonic liking components (the reduction of negative emotions and compensation for low self-worth), and the cognitive learning component (neurotic perfectionism). In this article, I link the theory of work craving with the theory of motivation and the incentive-sensitization theory of addiction and discuss three major issues: (a) obsessive-compulsive symptoms are not sufficient to diagnose workaholism; (b) two hedonic components of work craving, namely, activity-related and purpose-related incentives, should be considered; and (c) incentive-sensitization is an additional mechanism that may be prepotent for addictive working.

On the risk of dependence on gabapentinoids

In the last ten years, the prescriptions of the gabapentinoids gabapentin and pregabalin increased largely also in Germany. Since several national and international pharmacovigilance-databases have warned for abuse liabilities and overdose fatalities in association with both gabapentinoids, which moreover, became to be sold on internet and black-markets, their addictive power has been subject to an ongoing clinical debate. As pre- and post-approval clinical trials did not reveal significant signs of dependence on gabapentin or pregabalin, we systematically searched in PubMed and Scopus for clinical studies and case reports being associated with abuse of and dependence on these drugs. We found 14 clinical-epidemiologic studies and 38 case reports/series. These were evaluated for i) fulfilled dependence criteria according to ICD-10, ii) non-medical self-administration and their duration, iii) relapses, iv) social sequels, and v) cases seeking treatment for misusing gabapentin or pregabalin. Mostly, the cases of abuse of and dependence on gabapentinoids appeared to be associated with other substance dependencies, primarily opiate dependence and polyvalent drug use. Drug users preferred pregabalin citing a faster and stronger euphoria ("liking") than achievable with oral gabapentin. Both gabapentinoids were anxiolytic in therapeutic doses, stimulating in lower and sedating along with increasing doses. Fatalities have been described mainly in the population of opiate dependents and polyvalent drug users, predominantly together with excessive pregabalin overdosing. It is debated whether the gabapentinoids were indeed the main cause of death in these cases or whether gabapentin and pregabalin had been only bystanders. Tolerance and withdrawal symptoms (physical dependence) of gabapentinoids appeared to be common in medical and non-medical use of gabapentinoids. There were only 4 persons who had fulfilled behavioral dependence criteria of gabapentinoids (all had used pregabalin) and had no association with other substance use disorders (apart from nicotine). Regarding the transitions from prescription to non-medical self-administration, the frequency and duration of self-administrations as well as the number of reported relapses, pregabalin appeared also to be more addictive than gabapentin. However, all these events were reported rather infrequently compared with traditional substances of abuse. We did not find a case with social sequalea due to the use of gabapentinoids or a person who sought treatment for his gabapentin or pregabalin use. Therefore, the gabapentinoids were assumed to possess a lower "wanting" in consideration of Berridge's and Robinsons's incentive-sensitization theory of addiction. Also, anti-adverse selection of gabapentinoids is discussed to be present in the population of opioid and multi-drug users. Based upon all these results and assumptions, we have estimated the relative risk of dependence on gabapentinoids by using an algorithm which was previously developed by Griffith and Johnson for evaluation of the abuse liabilities of sedatives. Overall, the risk of harm and dependence on gabapentinoids appeared to be lower than that of other sedatives (and stimulants). In addition, pregabalin appeared to be somewhat riskier than gabapentin. We think that in patients with current or past substance use disorders, the treatment with gabapentinoids should be avoided or if indispensable, these drugs should be administered exclusively over a limited time span with caution by using a therapeutic and prescription monitoring.

Neural substrates of cue reactivity and craving in gambling disorder

Cue reactivity is an established procedure in addictions research for examining the subjective experience and neural basis of craving. This experiment sought to quantify cue-related brain responses in gambling disorder using personally tailored cues in conjunction with subjective craving, as well as a comparison with appetitive non-gambling stimuli. Participants with gambling disorder (n=19) attending treatment and 19 controls viewed personally tailored blocks of gambling-related cues, as well as neutral cues and highly appetitive (food) images during a functional magnetic resonance imaging (fMRI) scan performed ~2–3 h after a usual meal. fMRI analysis examined cue-related brain activity, cue-related changes in connectivity and associations with block-by-block craving ratings. Craving ratings in the participants with gambling disorder increased following gambling cues compared with non-gambling cues. fMRI analysis revealed group differences in left insula and anterior cingulate cortex, with the gambling disorder group showing greater reactivity to the gambling cues, but no differences to the food cues. In participants with gambling disorder, craving to gamble correlated positively with gambling cue-related activity in the bilateral insula and ventral striatum, and negatively with functional connectivity between the ventral striatum and the medial prefrontal cortex. Gambling cues, but not food cues, elicit increased brain responses in reward-related circuitry in individuals with gambling disorder (compared with controls), providing support for the incentive sensitization theory of addiction. Activity in the insula co-varied with craving intensity, and may be a target for interventions.

Liking, wanting, and the incentive-sensitization theory of addiction.

Rewards are both "liked" and "wanted," and those 2 words seem almost interchangeable. However, the brain circuitry that mediates the psychological process of "wanting" a particular reward is dissociable from circuitry that mediates the degree to which it is "liked." Incentive salience or "wanting," a form of motivation, is generated by large and robust neural systems that include mesolimbic dopamine. By comparison, "liking," or the actual pleasurable impact of reward consumption, is mediated by smaller and fragile neural systems, and is not dependent on dopamine. The incentive-sensitization theory posits the essence of drug addiction to be excessive amplification specifically of psychological "wanting," especially triggered by cues, without necessarily an amplification of "liking." This is because of long-lasting changes in dopamine-related motivation systems of susceptible individuals, called "neural sensitization." A quarter-century after its proposal, evidence has continued to grow in support the incentive-sensitization theory. Further, its scope is now expanding to include diverse behavioral addictions and other psychopathologies. (PsycINFO Database Record

Is Alcohol Addiction Usefully Called a Disease?

Is Alcohol Addiction Usefully Called a Disease? Nick Heather (bio) Keywords Alcoholism, problem drinking, disease concept, public health perspective, treatment, prevention, policy Gabriel Segal presents a defense of the disease concept of alcoholism against criticisms, including some of those by Ian Robertson and me (Heather and Robertson 1997). There is much to admire in this defense and much to agree with. I agree with Segal that some of the alternatives to the disease model that have been offered under the banner of ‘choice models’ of addiction (e.g., Davies 1997; Heyman 2009) fail to confront the baffling nature of addictive behavior or the fact that it is sometimes continued in the face of truly devastating consequences. Regarding the ‘two extreme pictures’ of alcohol addiction Segal sketches in his concluding section—the one where it is simply a matter of bad choices and the other where it is the result of absolutely irresistible urges—we both find ourselves in the middle ground. But that still leaves plenty of room for differences between us and disagreement in particular about one main issue, namely, whether alcoholism or problem drinking (Segal uses these terms interchangeably) is best viewed as a disease. Segal’s own model of alcoholism as a disease is highly idiosyncratic and would surely be disavowed by most proponents of a disease perspective on alcoholism, including, one suspects, the great majority of affiliates of the fellowship of Alcoholics Anonymous (AA). He strips away from the disease concept almost all the features that have previously been seen as essential to it. Thus, for Segal, it is no longer necessary that problem drinking is chronic, irreversible, or progressive; and alcoholics are not physically dependent on alcohol, can recover without treatment or a recovery program, and can be held legally or morally responsible for their drinking and its consequences. Perhaps most surprisingly, in view of his enthusiasm for Robinson and Berridge’s (1993) incentive sensitization theory of addiction, alcoholism is not a brain disease. (Since the rise of neuroscience, the idea that addiction, including alcohol addiction, is a disease of the brain has been the most powerful, influential, and research-based version of the disease perspective and the incentive sensitization theory is one of the leading expressions of that idea.) The main point here, however, is that, having given up most of the requirements that previous theorists have seen as being entailed in regarding alcoholism a disease and having thereby conceded most of the key arguments of its opponents, one wonders what is meaningfully left and why Segal continues to believe that problem drinking is a disease rather than join those see the limitations of this belief. [End Page 321] One conventional property of a disease that remains in Segal’s account is that alcoholism is allor-none; although among those having the disease it comes in degrees, you either have alcoholism or you do not. This is indeed one of the key points dividing supporters and opponents of the disease concept of alcoholism. In this case, however, Segal’s adherence to the discrete nature of the condition leads him into difficulties. We are told that there exists a large group of heavy drinkers who may drink more than a mild alcoholic, but who are not themselves alcoholics. This is because they do not show what, for Segal, are the key symptoms of the disease of alcoholism: craving, preoccupation with alcohol, and impaired control over drinking, symptoms that can range in severity from mild to severe. The difficulty here is that it is easy to show that these ‘symptoms’ exist on continua throughout the population of regular and heavy drinkers; almost all such individuals would obtain positive scores, for example, on measures of alcohol dependence that assess degrees of desire for and preoccupation with alcohol (e.g., Raistrick et al. 1994) or measures of impaired control over drinking (Heather, Booth and Luce 1998), even those who show no obvious alcohol-related problems. (Ironically, Segal refers to the latter instrument to support his view that impaired control is specific to those suffering from the disease of alcoholism, whereas our recommendation to its users was that it was relevant to all regular drinkers.) To suggest that all...

Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery

The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking.

Brain activity during anticipation of smoking-related and emotionally positive pictures in smokers and nonsmokers: A new measure of cue reactivity

Previous studies have shown that a brain wave pattern known as stimulus preceding negativity (SPN) can index the anticipation of motivationally relevant events. The present study was the first to use SPN as an index of the motivational significance of smoking-related pictures. Emotionally positive and neutral pictures served as controls. The paradigm involved the following sequence: (a) presentation of a picture (S1) for 500 ms, (b) a fixation cross for 3,500 ms, (c) a second presentation (S2) of the same picture for 2,000 ms, and (d) another fixation cross signifying the beginning of a new S1-S2 trial using a different picture. The participants (N = 24, half smokers and half nonsmokers) viewed pictures from three categories (smoking-related, emotionally positive, or emotionally neutral). Consistent with predictions, smokers exhibited significantly greater mean SPN amplitudes in anticipation of smoking-related pictures relative to neutral pictures. Among nonsmokers the SPN was significantly smaller in anticipation of smoking pictures compared with neutral pictures. These findings are consistent with the incentive sensitization theory of addiction and other conditioning and cue-reactivity models.

The incentive sensitization theory of addiction: some current issues

We present a brief overview of the incentive sensitization theory of addiction. This posits that addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. If rendered hypersensitive, these systems cause pathological incentive motivation ('wanting') for drugs. We address some current questions including: what is the role of learning in incentive sensitization and addiction? Does incentive sensitization occur in human addicts? Is the development of addiction-like behaviour in animals associated with sensitization? What is the best way to model addiction symptoms using animal models? And, finally, what are the roles of affective pleasure or withdrawal in addiction?

Subjective responses to initial experience with cocaine: an exploration of the incentive–sensitization theory of drug abuse

This study investigated the relationship between positive and negative subjective responses at the time of initial cocaine use with adult cocaine dependence and life-time use rates. Psychostimulant pre-exposure, regular smoking or stimulant treatment before initiation were examined to explore the incentive sensitization theory of addiction. A total of 202 adult participants who had tried cocaine on at least one occasion were studied prospectively from childhood into adulthood. The cocaine-initiated group included 89 who met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for attention deficit hyperactive disorder (ADHD) and 113 age-matched controls. Five childhood and three adulthood interviews provided data on ages of initiation into cocaine and life-time use of cocaine from ages 16-40 years. Correlations of each subjective response and analyses of variance (ANOVAs) of cocaine 'liking' and 'wanting' with DSM-III-R cocaine dependence and life-time use provided support for the validity of the measures. ANOVA provided evidence of the effect of psychostimulant pre-exposure on 'liking' and 'wanting'. Logistic regression modeled the prediction of dependence and life-time use with the independent variables of 'liking' and 'wanting', psychostimulant pre-exposure and participant characteristics. When cocaine was first tried, 'liking' and 'wanting' were significant predictors of cocaine dependence and life-time use. Mean 'liking' or 'wanting' responses did not differ by participant characteristics. Those who were pre-exposed by regular smoking or stimulant treatment had higher 'liking' and 'wanting' scores; but participants who were pre-exposed by both stimulant treatment and regular smoking reported the lowest liking and the highest wanting responses, consistent with the incentive sensitization theory. Logistic regression showed that the 'liking' and 'wanting' responses increased significantly the odds of DSM-III-R cocaine dependence and life-time use. In this sample, subjective 'liking' and 'wanting' measured risk for cocaine abuse.

The psychology and neurobiology of addiction: an incentive-sensitization view.

The question of addiction specifically concerns (1), the process by which drug-taking behavior, in certain individuals, evolves into compulsive patterns of drug-seeking and drug-taking behavior that take place at the expense of most other activities and (2), the inability to cease drug-taking; the problem of relapse. In this paper current biopsychological views of addiction are critically evaluated in light of the "incentive-sensitization theory of addiction", which we first proposed in 1993, and new developments in research are incorporated. We argue that traditional negative reinforcement, positive reinforcement, and hedonic accounts of addiction are neither necessary nor sufficient to account for compulsive patterns of drug-seeking and drug-taking behavior. Four major tenets of the incentive-sensitization view are discussed. These are: (1) Potentially addictive drugs share the ability to produce long-lasting adaptations in neural systems. (2) The brain systems that are changed include those normally involved in the process of incentive motivation and reward. (3) The critical neuroadaptations for addiction render these brain reward systems hypersensitive ("sensitized") to drugs and drug-associated stimuli. (4) The brain systems that are sensitized do not mediate the pleasurable or euphoric effects of drugs (drug "liking"), but instead they mediate a subcomponent of reward we have termed incentive salience (drug "wanting"). We also discuss the role that mesolimbic dopamine systems play in reward, evidence that neural sensitization happens in humans, and the implications of incentive-sensitization for the development of therapies in the treatment of addiction.

Subject index

Addiction follows a chronic course, with periods of absti­nence followed by relapse. Vulnerability to relapse can persist even after years of abstinence, suggesting that long-lasting and perhaps permanent neurobiological changes underlie addiction. The incentive-sensitization theory of addiction pro­poses that sensitization occurs in the neural systems that attribute incentive salience to drugs and drug-associated cues. Alternatively, addiction is characterized as a spiraling cycle of hedonic dysregulation driven by many factors, but with an important role ascribed to negative affective states that occurs during periods of drug abstinence. There are tremendous individual differences in vulnerability, reflecting both genetic and environmental influences, and many people experiment with potentially addictive drugs without progressing to compulsive use. Long-term drug exposure produces many physiologi­cal and behavioral changes that contribute to addiction. Tolerance is the need for increasing doses of a drug to achieve the same effect. Sensitization refers to the enhancement of drug responses as a result of repeated drug exposure. For a given drug, it is possible for certain effects to show tol­erance and others to show sensitization. Dependence is an adapted physiological state of cells or systems that devel­ops to compensate for excessive stimulation by a drug.