Addiction (2001) 96, 103–114

MECHANISMS OF ACTION OF ADDICTIVE STIMULI

Incentive-sensitization and addiction

TERRY E. ROBINSON & KENT C. BERRIDGE

Department of Psychology (Biopsychology Program), The University of Michigan, Ann Arbor, MI, USA

Abstract The question of addiction concerns 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 the inability to cease drug-taking, that is, the problem of relapse. In this paper we summarize one view of this process, the “incentive-sensitization” view, which we Ž rst proposed in 1993. Four major tenets of the incentive-sensitization view are discussed. These are: (1) potentially addictive drugs share the ability to alter brain organization; (2) the brain systems that are altered 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; and (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”).

Introduction acterizes addiction often are not motivated by Most contemporary explanations of addiction either the desire to obtain pleasure or by posit that addicts are motivated to take drugs the desire to relieve withdrawal (see Robinson primarily for one of two reasons, by “the desire & Berridge, 1993 and 2000, for a critique of to experience the positive hedonic effects of withdrawal avoidence and pleasure-seeking the drug … and the desire to avoid aversive views of addiction). If this is true, then why do withdrawal symptoms …” (Markou et al., addicts compulsively seek drugs? We have at- 1993, p. 176). In other words, it is generally tempted to address this question by proposing thought that addicts are motivated to take drugs the concept of “incentive-sensitization” either for the pleasure drugs produce (basically (Robinson & Berridge, 1993, 2000; Berridge & to achieve remembered pleasure), or to avoid Robinson, 1995), which can be summarized in the unpleasant consequences of withdrawal. four points. We have argued, however, that the compulsive drug-seeking and drug-taking behavior that char- (1) Potentially addictive drugs share the ability

This paper is an abbreviated version of ‘The Psychology and Neurobiology of Addiction: An Incentive-Sensitiza- tion View’, which was published earlier in a special supplement of Addiction. (Vol. 95, Supplement 2, 2000). Correspondence to: Dr Terry E. Robinson, Department of Psychology (Biopsychology Program), The University of Michigan, 525 E. University (East Hall), Ann Arbor, MI 48109, USA. Tel: (734) 763 4361; fax: (734) 763 7480; e-mail: [email protected] Submitted 28th October 1999; initial review completed 17th December 1999; Ž nal version accepted 2nd June 2000.

ISSN 0965–2140 print/ISSN 1360–0443 online/01/010103–12 Ó Society for the Study of Addiction to Alcohol and Other Drugs

Carfax Publishing, Taylor & Francis Limited DOI: 10.1080/09652140020016996 104 Terry E. Robinson & Kent C. Berridge

to produce long-lasting changes in brain or- mediates these effects is either the same as, or at ganization. least overlaps with, the neural substrate respon- (2) The brain systems that are changed include sible for the rewarding effects of drugs (Wise & those normally involved in the process of Bozarth, 1987). This neural substrate is, of incentive motivation and reward. course, the mesotelencephalic dopamine system, (3) The critical neuroadaptations for addiction and especially dopamine projections to the render these brain reward systems hypersen- nucleus accumbens and accumbens-related cir- sitive (“sensitized”) to drugs and drug-asso- cuitry (often called the mesolimbic or mesocorti- ciated stimuli. colimbic dopamine system). (4) The brain systems that are sensitized do not There is now a wealth of evidence showing mediate the pleasurable or euphoric effects that the repeated intermittent administration of a of drugs (drug “liking”), but instead they variety of drugs of abuse results in a progressive mediate a subcomponent of reward we have increase in their psychomotor activating effects, termed incentive salience or “wanting” and although most studies of psychomotor sensi- (Berridge, Venier & Robinson, 1989; tization involve the administration of psychomo- Berridge & Valenstein, 1991; Robinson & tor stimulants, such as amphetamine or cocaine, Berridge, 1993; Berridge & Robinson, 1995, psychomotor sensitization has been reported 1998; Berridge, 1996). We posit the psycho- with methylphenidate, fencamfamine, morphine, logical process of incentive salience to be phencyclidine, MDMA, nicotine and ethanol speciŽ cally responsible for instrumental (Robinson, 1993; Robinson & Berridge, 2000; drug-seeking and drug-taking behavior (drug for references). Psychomotor sensitization is a “wanting”). very complex and rich phenomenon. For exam- ple, it is dose-dependent (Kalivas et al., 1988; We have hypothesized that when sensitized, this Browman, Badiani & Robinson, 1998a, 1998b), incentive salience process produces compulsive it is usually seen only when drugs are adminis- patterns of drug-seeking behavior (Robinson & tered intermittently (Post, 1980, Robinson & Berridge, 1993; Berridge & Robinson, 1995). Becker, 1986), it is often more evident long after Through associative learning the enhanced in- the discontinuation of repeated drug treatment centive value becomes focused speciŽ cally on than shortly after the discontinuation of drug drug-related stimuli, leading to increasingly com- treatment (Antelman, 1988), and perhaps the pulsive patterns of drug-seeking and drug-taking most remarkable feature of sensitization is its behavior. Furthermore, the persistence of neural persistence. Once sensitized, animals may re- sensitization is hypothesized to leave addicts sus- main hypersensitive to the psychomotor activat- ceptible to relapse even long after the discontinu- ing effects of drugs for months or years ation of drug use. In the following we will review (Robinson & Becker 1986; Paulson, Camp & brie y some of the evidence for incentive-sensi- Robinson, 1991). Finally, sensitization is seen tization, and elaborate some of the major fea- not only following experimenter-administered tures of this view of addiction. drug, but drug self-administration experience can also induce psychomotor sensitization (Hooks et al., 1994; Phillips & Di Ciano, 1996; Psychomotor sensitization Marinelli, Le Moal & Piazza,1998). Most studies showing that the repeated adminis- Two other important features of sensitization tration of drugs of abuse can produce sensitiza- deserve mention. One is that there is enormous tion (i.e. an increase in drug effect) involve individual variation in susceptibility to sensitiza- measures of the psychomotor activating effects of tion (Robinson, 1988). Some individuals show drugs, such as their ability to enhance locomotor rapid and robust sensitization with a given dose activity, rotational behavior or stereotyped motor of a drug, whereas others sensitize very little, if at patterns (Segal, Geyer & Schuckit, 1981; all. There are many factors that contribute to Robinson & Becker, 1986; Robinson & Berridge, individual variation in the susceptibility to sensi- 1993; Stewart & Badiani, 1993). Studies on the tization, including genetic, hormonal and experi- psychomotor activating effects of drugs are ential factors (Shuster, Yu & Bates, 1977; thought to be relevant to addiction because of Antelman et al., 1980; Robinson, 1988), al- the assumption that the neural substrate that though how they do so is largely unknown. Incentive-sensitization and addiction 105

Nevertheless, the incentive-sensitization theory administration (Anagnostaras & Robinson, posits that factors which render people suscep- 1996). Indeed, it needs to be remembered that tible to sensitization will also contribute to indi- the ability of sensitized neural systems to gain vidual variation in susceptibility to addiction. control over behavior is constantly modulated or Another important feature of psychomotor gated by environmental (and probably interocep- sensitization is that it is not an inevitable conse- tive) stimuli that have been associated with drug quence of repeated exposure to drugs. Instead, administration. It may be that this interaction of the ability of drugs to induce or express sensitiza- neural sensitization with associative learning is tion is powerfully modulated by learning and the responsible for the focus on drug-associated circumstances surrounding drug administration stimuli in addicts, whereby the acts and objects (Robinson et al., 1998). There are at least two associated with drug-taking become especially ways that the circumstances surrounding drug powerful incentives themselves. Contextual administration modulate sensitization. The Ž rst modulation of the expression of sensitization is modulation of the expression of neural sensi- may contribute to the critical role that context tization that has already been induced. Perhaps plays in precipitating relapse. That is, an impli- the best example of environmental modulation of cation for addiction is that the expression of expression is the phenomenon of context-speciŽ c sensitization to the incentive properties of drug- sensitization. This refers to the observation that related stimuli may be strongest in contexts that if animals are tested (i.e. receive a drug chal- have been also distinctly related to drug-taking in lenge) in an environment different from the one the past. The ability of context to act as an in which they received prior drug treatments, occasion-setter and to modulate sensitization sensitization is often not expressed in behavior would interact with the ability of speciŽ c drug- (Post et al., 1981; Pert, Post & Weiss, 1990; associated conditioned stimuli to trigger craving Anagnostaras & Robinson, 1996; Terelli & as a classically conditioned response, combining Terry, 1999). Despite this powerful conditioned to provide very strong contextual control over stimulus control over the expression of behavioral both craving and relapse (Robinson & Berridge, sensitization there are at least two reasons to 1993; Anagnostaras & Robinson, 1996; believe that in this situation neural sensitization Robinson & Berridge, 2000). has developed, even though animals do not ex- The second way in which the circumstances press it in behavior. The Ž rst is that animals surrounding drug administration may modulate receiving drug treatments in an environment sensitization is to in uence whether neural sensi- other than the test environment develop normal tization is induced in the Ž rst place (or at least behavioral sensitization in their drug treatment the rate and extent of sensitization produced by environment; they simply do not express it in a a given dose of a drug). For example, there are different environment that has never been paired now a number of reports that when low to with drug administration (Anagnostaras & moderate doses of amphetamine or cocaine are Robinson, 1996). Secondly, neural sensitization administered in the environment where an ani- has been described under conditions that pre- mal lives (i.e. at “home”) they are less effective clude the in uence of contextual stimuli on the in inducing psychomotor sensitization than if the neurobiological expression of the drug response, same doses are given in a relatively distinct test for example, in striatal tissue slices in vitro or in environment (one that is novel to the animal anesthetized animals (Robinson & Becker, 1982; until its Ž rst pairing with the drug; Badiani, Castan˜eda, Becker & Robinson, 1988; Henry & Anagnostaras & Robinson, 1995; Badiani, Brow- White, 1991; Nestby, Vanderschuren & De man & Robinson, 1995; Crombag, Badiani & Vries, 1997; Kantor, Hewlett & Gnegy, 1999; Robinson, 1996; Badiani, Camp & Robinson, Vanderschuren et al., 1999a). 1997; Browman, Badiani & Robinson, 1998a; It appears, therefore, that repeated exposure to Robinson et al., 1998; Fraioli et al., 1999). Fur- amphetamine may induce neural sensitization ther studies have established that the effect of non-associatively, but whether the consequences environmental context is not to completely pre- of neural sensitization are expressed at a particular clude sensitization, but to shift the dose-effect place or time is determined to a large extent by curve for the induction of sensitization. When conditional stimuli (especially contextual stim- high enough doses of either cocaine or am- uli) that have been associatively paired with drug phetamine are given sensitization is induced re- 106 Terry E. Robinson & Kent C. Berridge gardless of environmental condition (Browman & Schenk, 1990; Horger, Giles & Schenk, 1992; et al., 1998a, 1998b). Valadez & Schenk, 1994; Pierre & Vezina, 1997; The ability of environmental context to modu- Pierre & Vezina, 1998) or a conditioned place late the induction of sensitization may be related preference (Lett, 1989; Gaiardi et al., 1991; to its ability to modulate the neural circuitry Shippenberg & Heidbreder, 1995; Shippenberg, engaged by drugs. Badiani and colleagues (1998) Heidbreder & Lefevour, 1996; Shippenberg, reported, for example, that the ability of am- Lefevour & Heidbreder, 1996). Previous sensi- phetamine to induce c-fos mRNA in the striatum tization to amphetamine also increases the is modulated powerfully by the environmental “breakpoint” for amphetamine self-administra- context in which amphetamine is administered. tion when rats are tested using a progressive ratio Indeed, it appears that that environmental con- schedule (Mendrek, Blaha & Phillips, 1998; Lor- text can modulate which cell populations in the rain, Arnold & Vezina, 2000), and the enhanced striatum are engaged by amphetamine. When responding for a conditioned reward produced given at home amphetamine induced c-fos only by intra-accumbens amphetamine is potentiated in striatal neurons also positive for dopamine D1 by cocaine sensitization (Taylor & Horger, receptor mRNA (not in cells positive for D2 1999). Furthermore, sensitization to am- receptor mRNA). However, when given in as- phetamine facilitates behavior guided by Pavlo- sociation with environmental novelty am- vian learning (Harmer et al., 1997; Harmer & phetamine induced c-fos in both D1 and D2 Phillips, 1998, 1999a, 1999b). Finally, in recent mRNA-positive neurons (Badiani et al., 1999). studies Deroche, Le Moal & Piazza (1999) have In summary, sensitization is not an inevitable found that experience with self-administered co- consequence of exposure to potentially addictive caine later enhances the motivation to seek drugs. That is, it is not a simple pharmacological cocaine in, for example, a runway apparatus, and phenomenon. Both the expression and the in- De Vries and colleagues in the Netherlands have duction of sensitization can be powerfully modu- reported that the ability of different drugs to lated by non-pharmacological factors, including reinstate (prime) drug-seeking behavior is related environmental factors associated with drug ad- positively to whether they also show cross-psy- ministration. The in uence of environmental chomotor sensitization (De Vries et al., 1997, factors on sensitization has important implica- 1998, 1999; Vanderschuren et al., 1999b). tions not only for understanding the phenom- The second line of evidence that the neural enon, but for thinking about therapeutic substrate sensitized by drugs of abuse is involved approaches in treating addiction. in mediating drug reward, comes from studies on the neurobiology of sensitization. There is not space here to review this large literature, but Sensitization and drug reward sufŽ ce to say there is now considerable evidence The studies reviewed above on sensitization to that behavioral sensitization is associated with the psychomotor activating effects of drugs indi- neuroadaptations in dopamine and accumbens- cate that addictive drugs induce neural sensitiza- related circuitry (Robinson & Becker, 1986; tion; but by themselves they provide only Kalivas & Stewart, 1991; Robinson & Berridge, indirect evidence that sensitization occurs to the 1993; Stewart & Badiani, 1993; Pierce & Kali- incentive motivational or rewarding effects of vas, 1997; White & Kalivas, 1998; Wolf, 1998). drugs (Wise & Bozarth, 1987). More direct evi- This is important because it is well established dence that the neural substrate that is sensitized that these neural systems play an important role is involved in mediating drug reward comes from in mediating the rewarding effects of drugs and two other sources. The Ž rst are studies showing other incentives (Wise & Bozarth, 1987; Koob & that not only do the psychomotor stimulant ef- Bloom, 1988; Smith, 1995). Thus, if sensitiza- fects of drugs sensitize, but so do their rewarding tion-related neuroadaptations are found in this effects (Schenk & Partridge, 1997). There are a mesocorticolimbic circuitry this is strong evi- number of reports that prior exposure to a var- dence that at least one neural system known to iety of potentially addictive drugs enhances the be critical for mediating drug reward undergoes later acquisition of both a drug self-administra- “neural sensitization”. tion habit (Woolverton, Goldberg & Ginos, Both pre- and post-synaptic neuroplastic 1984; Piazza et al., 1989, 1990; Horger, Shelton adaptations have been described in the Incentive-sensitization and addiction 107 dopamine/accumbens system of sensitized ani- drug reward that with repeated drug use drugs mals. An example of a presynaptic adaptation is gradually become more and more attractive (i.e. a persistent increase in the ability of a variety of they acquire greater and greater incentive value), drugs to increase the over ow of dopamine in and become increasingly able to control behav- the nucleus accumbens and striatum of sensi- ior. Studies on sensitization of drug reward and tized animals, in vitro and in vivo (Robinson & the neurobiology of sensitization support this Becker, 1982, 1986; Kalivas & Stewart, 1991; claim. Furthermore, we have suggested that sen- Robinson & Berridge, 1993; Nestby et al., 1997; sitization enhances the probability of relapse, Pierce & Kalivas, 1997; Kantor et al., 1999; even long after the discontinuation of drug use, Vanderschuren et al., 1999a). Examples of post- and animal studies on the relationship between synaptic adaptations include an increase in the psychomotor sensitization and reinstatement sensitivity of dopamine D1 receptors (Henry & support this claim. Of course, the hypothesis that White, 1991; White & Kalivas, 1998) and a incentive-sensitization mediates addiction in hu- decrease in the sensitivity of glutamate receptors mans is more speculative, and is predicated on (White et al., 1995) in the nucleus accumbens of the assumption that repeated exposure to drugs sensitized animals (see Clark & Overton, 1998; of abuse can induce neural sensitization in hu- Wolf, 1998 for a review of the role of excitatory mans. It is one thing to demonstrate incentive- amino acids in sensitization). More recently it sensitization in animals models, but—as critics of has been reported that both amphetamine and our theory occasionally point out—quite another cocaine sensitization are also accompanied by to demonstrate its occurrence in addicts. persistent structural modiŽ cations in the mor- phology of output neurons in both the nucleus accumbens and prefrontal cortex (Robinson & Sensitization in humans Kolb, 1997, 1999). Repeated treatment with As might be expected from the difŽ culty in amphetamine or cocaine increases the length of studying this issue in humans, there has been dendrites on medium spiny neurons in the nu- very little research on the topic of whether sensi- cleus accumbens and on pyramidal neurons in tization actually occurs in the brains of human the prefrontal cortex. This is accompanied by an addicts. Until recently, the only direct evidence increase in spine density on the distal dendrites that repeated exposure to psychostimulant drugs of these cells. On medium spiny neurons there is can produce sensitization in humans came from an especially large increase in the number of studies on the phenomenology of amphetamine branched spines; that is, spines with multiple and cocaine psychosis (Post & Contel, 1983; heads. Furthermore, cocaine self-administration Segal & Schuckit, 1983; Sato et al., 1983; Sato, experience has similar effects (Robinson et al., 1986; Angrist, 1994). There is a considerable 1999). These data suggest that sensitization may clinical literature which suggests that repeated involve changes in patterns of synaptic connec- exposure to amphetamine or cocaine results in a tivity in brain reward systems, changes that may progressive increase in their psychotomimetic be similar to those seen in other neural systems effects (Angrist, 1994), and that this enhanced in association with other forms of experience- sensitivity may persist long after the discontinu- dependent plasticity (Robinson & Kolb, 1997, ation of drug use (Utena, 1966; Sato et al., 1983; 1999). Sato, 1986). Related effects have been described To reiterate the basic thesis of the incentive- in non-human primates (Castner & Goldman- sensitization view of addiction, it was originally Rakic, 1999). proposed (Robinson & Berridge, 1993) that ad- More direct evidence for sensitization to the dictive drugs share the ability to produce persist- psychomotor effects of amphetamine in humans ent neuroadaptations in brain regions involved in has been lacking until only very recently, but the process of incentive motivation and reward, there are now two reports of psychomotor sensi- adaptations that render these regions hypersensi- tization in humans. Strakowski et al. (1996) Ž rst tive (“sensitized”). It should be clear from the reported the results of a double-blind, placebo- above that there is now a wealth of evidence to controlled study in drug-naive volunteers given support this claim. The incentive-sensitization two treatments (48 hours apart) with 0.25 mg/kg view also posits that it is largely because of d-amphetamine. They found that the second sensitization of a neural substrate that mediates treatment with amphetamine elicited a 108 Terry E. Robinson & Kent C. Berridge signiŽ cantly greater increase than the Ž rst in four makes strong predictions regarding neural sensi- behavioral measures: activity/energy, mood, rate tization and drug-seeking in human addicts, but and amount of speech and eye-blink rate. In a not necessarily about what which speciŽ c observ- second study Strakowski & Sax (1998) replicated able other behaviors might best re ect neural and extended these Ž ndings to see if three treat- sensitization. The critical prediction made by the ments with amphetamine would produce a pro- incentive-sensitization view of addiction is this: gressive increase in drug effect, as is usually seen the brains of human addicts who compulsively in animal experiments. Two measures increased crave drugs will contain a neural substrate that progressively with repeated amphetamine treat- has been rendered sensitized by drugs. A role of ment: activity/energy and eye-blink rate. Indeed, that neural substrate will be to mediate the in- for eye-blink rate there was no effect of the Ž rst centive salience of drug rewards. Further, indi- treatment with amphetamine, relative to placebo, viduals will differ in their susceptibility for but an increase in eye-blink rate emerged with sensitization of that neural substrate, and those subsequent drug treatments even though the who sensitize most readily will be most at risk for dose was the same. Finally, evidence supporting addiction. These predictions are testable, and so the concept of incentive-sensitization in humans, the incentive sensitization theory of addiction relevant speciŽ cally to drug taking, comes from can be conŽ rmed or disproved on the basis of the interesting tentative observation of Bartlett et empirical evidence. al. (1997) that cocaine users who developed A better understanding of the nature of neural sensitization to the psychotomimetic effects of sensitization, based on animal studies, will be the drug have an elevated incidence of relapse, as crucial to developing proper tests of the theory in indicated by more frequent rehospitalizations. human addicts. Once we understand the neural In summary, although there is little research in basis of sensitization in non-human animals we humans and it is fraught with technical limita- should be able to determine if the same neuroad- tions, the available evidence suggests that re- aptions exist in the brains of addicts. If they do peated exposure to psychostimulant drugs can not, the incentive-sensitization theory is proved sensitize some drug effects in humans. Further wrong. Of course, this proof Ž rst requires that studies on behavioral sensitization in humans we understand which neurobiological adapta- will be critical in testing the notion of incentive- tions produced by repeated treatment with drugs sensitization, but it is worth injecting a note of are causally related to the sensitization of which caution in interpreting negative behavioral stud- behaviors. Secondly, it will require that adequate ies. It is not obvious a priori which behavioral technological tools be developed to quantify the measures in humans will provide the most sensi- relevant neuroadaptations, in the relevant brain tive indicators of a sensitization process. This is regions in humans, which given the rapid ad- a difŽ cult issue even in animal studies. For ex- vances in this Ž eld, should appear in the future. ample, it is often difŽ cult to quantify behavioral Thus, future research on neuroadaptations en- sensitization using measures of locomotor ac- gendered by drug use in humans, derived from tivity, unless exactly the right dose and treatment an understanding of the development of neural conditions are used (Crombag et al., 1999). sensitization in animal models, will eventually Also, even in rats, some behaviors show robust provide a Ž nal test of the notion of incentive-sen- sensitization, such as rotational behavior, repeti- sitization. tive snifŽ ng and repetitive head movements, whereas other seemingly related stereotyped be- haviors do not, such as oral movements “Wanting” versus “Liking” (Robinson & Becker, 1986; Crombag et al., The Ž nal issue we would like to address concerns 1999). the nature of the psychological process that is Finally, one needs to keep in mind that for the mediated by the neural substrate that undergoes most part indices of behavioral sensitization are sensitization. To the extent this is the dopamine/ important only as secondary measures because accumbens system it concerns the nature of the they provide indicators of underlying neuroadap- incentive and reward function mediated by this tive processes (neural sensitization), and it is circuitry. This leads us to the topic that we have neural sensitization that we posit to be crucial to termed “wanting” versus “liking” (Berridge & addiction. The incentive-sensitization hypothesis Valenstein, 1991; Robinson & Berridge, 1993; Incentive-sensitization and addiction 109

Berridge & Robinson, 1995, 1998; Berridge, both in non-human animals (Berridge et al., 1996, 1999). The incentive-sensitization theory 1989; Berridge, 1996; Berridge & Robinson, posits explicitly that hedonic affect, either as 1998) and in humans (Brauer & DeWit, 1996, subjective pleasure or its underlying core process 1997; Ohuoha et al., 1997) (see Berridge, 1996; (“liking”), is not the component of drug reward Berridge & Robinson, 1998) for extensive review that is sensitized in addiction, and is not the and discussion of this point). It is because of psychological process that is mediated by do- these kinds of experimentally established dissoci- pamine systems (Robinson & Berridge, 1993; ations between the apparent incentive value of Berridge, 1996; Berridge & Robinson, 1998). drugs (and natural rewards, such as food), and Instead, we have hypothesized that a different their ability to engender pleasure, that we sug- component of incentive motivation is sensitized gested a distinction be made between “wanting” in addiction, a component we have termed and liking” (Berridge & Valenstein, 1991; “wanting” (Robinson & Berridge, 1993; Robinson & Berridge, 1993; Berridge, 1996). Berridge, 1996; Berridge & Robinson, 1998). More speciŽ cally, we have hypothesized that The idea that the process of incentive motiv- the neural and psychological processes underly- ation can be subdivided into at least two compo- ing “wanting” involve the attribution of attract- nents is an extension of traditional psychological ive salience to stimuli and their representations, models of incentive motivation developed by the- a process we call incentive salience attribution. We orists such as Bindra (1978) and Toates (1986), have suggested it is the process of incentive and neurobiologically it is an extension of views salience attribution that transforms the sensory proposed by Phillips, Fibiger and colleagues features of ordinary stimuli or, more accurately, (Fibiger & Phillips, 1986; Blackburn et al., the neural and psychological representations of 1989), Wise (1985, 1989; Wise & Bozarth, stimuli, so that they become especially salient 1987) and Panksepp (1986a, 1986b). In tra- stimuli, stimuli that “grab the attention”, that ditional models of incentive motivation it was become especially attractive and wanted, thus hypothesized that a single process mediates both eliciting approach and guiding behavior to the incentive value (how much an incentive is goal (Robinson & Berridge, 1993; Berridge, “wanted”), and hedonic value (how much it is 1996; Berridge & Robinson, 1998). It is incen- “liked”). Incentives were hypothesized to have tive salience that determines the value of incen- incentive value because of their ability to produce tives, and that controls seeking and instrumental pleasure. Therefore, what we have called behavior regarding them (Berridge & Robinson, “wanting” and “liking” were necessarily connec- 1998). Thus, when the neural systems that me- ted and treated as explanations for positive re- diate incentive salience become sensitized, and if inforcement. There is evidence, however, that the incentive salience attributed to drug-taking the psychological process and neural substrate and to associated stimuli becomes pathologically responsible for motivating behavior, for deter- ampliŽ ed, then compulsive drug-seeking and mining incentive value (“wanting”), is separable drug-taking behavior may ensue. from the psychological process and neural sub- Finally, we have argued that the neural system strate that mediates hedonics (“liking”) responsible for incentive salience attribution can (Berridge & Valenstein, 1991; Robinson & sometimes produce goal-directed behavior Berridge, 1993; Berridge, 1996; Berridge & (“wanting”) not only in the absence of subjective Robinson, 1998). For example, drugs of abuse pleasure (e.g. Lamb et al., 1991), but in the ab- can promote drug-taking behavior in the absence sence of conscious awareness of “wanting” itself of any subjective hedonic effects (Fischman, (for a full discussion of this point see Robinson & 1989; Lamb et al., 1991; Fischman & Foltin, Berridge, 1993, 2000; Berridge & Robinson, 1992), which is not consistent with the notion 1995; Berridge, 1996, 1999). That is, activation that the positive reinforcing effects of drugs can of this system may constitute an implicit rather be equated with their hedonic impact. Further- than explicit psychological process, similar to more, there is considerable evidence that manip- implicit memory or to implicit perceptual pro- ulations of dopamine neurotransmission exert cesses (Tiffany, 1990; Weiskrantz, 1997), and powerful effects on motivated behavior can act sometimes as an unconscious motiva- (“wanting”) without changing basic hedonic re- tional process (Robinson & Berridge, 1993; actions (“liking”) to unconditioned rewards, Berridge & Robinson, 1995; Berridge, 1999). 110 Terry E. Robinson & Kent C. Berridge

We become aware of its activation only by en- ANTELMAN, S. M., EICHLER, A. J., BLACK, C. A. & gaging interpretive cognitive processes needed to KOCAN, D. (1980) Interchangeability of stress and amphetamine in sensitization, Science, 207, 329– translate implicit activation into explicit subjec- 331. tive feelings (Nisbett & Wilson, 1977; Hilgard, BADIANI, A., ANAGNOSTARAS , S. G. & ROBINSON, T. E. 1986; LeDoux, 1996; Berridge & Robinson, (1995) The development of sensitization to the psy- 1998). Indeed, it may be because these psycho- chomotor stimulant effects of amphetamine is en- logical processes sometimes operate outside of hanced in a novel environment, Psychopharmacology, 117, 443–452. conscious awareness that addicts have so little BADIANI, A., BROWMAN, K. E. & ROBINSON, T. E. insight into why they want drugs so much. 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