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American Psychologist

Manuscript version of

Liking, Wanting, and the Incentive-Sensitization Theory of Addiction

Kent C. Berridge, Terry E. Robinson

Funded by: • National Institutes of Health

© 2016, American Psychological Association. This manuscript is not the copy of record and may not exactly replicate the final, authoritative version of the article. Please do not copy or cite without authors’ permission. The final version of record is available via its DOI: https://dx.doi.org/10.1037/amp0000059

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Liking, Wanting and Addiction

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Liking, Wanting, and the Incentive-Sensitization Theory of Addiction

Kent C. Berridge and Terry E. Robinson

University of Michigan

Liking, Wanting and Addiction

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Abstract

Rewards are both ‘liked’ and ‘wanted’, and those two 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 due to 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.

Keywords: pleasure, desire, reward, addiction, motivation, brain, limbic, dopamine

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It is now widely accepted that brain mechanisms that determine how much a reward is

‘wanted’ are dissociable from those that determine how much the same reward is ‘liked’.

However, that idea, which we first proposed in 1989 as a post hoc explanation for some negative

results on the role of the brain’s mesolimbic dopamine system in pleasure (Berridge et al 1989),

originally came as a surprise even to us. At the time, we and most other investigators generally

accepted the idea that dopamine mediates reward pleasure: the hedonic impact of tasty food,

addictive drugs and many other rewards. Our early experiment was simply intended to provide

another bit of evidence for the dopamine-pleasure hypothesis -- but results turned out otherwise.

As background, many studies had found that brain dopamine systems were activated by

most rewards, and further that manipulating dopamine altered ‘wanting’ for rewards: for

example changing how much animals preferred, pursued, worked for, or consumed the reward

(Koob & Le Moal, 1997; Wise, 1985). Changes in ‘wanting’ were naturally interpreted to reflect

corresponding changes in ‘liking’, based on the assumption that ‘wanting’ was proportional to

‘liking’. Our approach to measuring pleasure impact was different, and more similar to how for

millennia parents have asked their newborn infants whether the taste of a particular food was

enjoyable. We used a naturalistic or ethological assay of sweetness pleasure, based on affective

facial expressions of ‘liking’ (Steiner, 1973). Sweetness elicits relaxed facial expressions and

rhythmic tongue and mouth expressions of ‘liking’, whereas bitterness elicits ‘disgust’ gapes and

turning away. Those affective facial expressions to taste are homologous in human infants, apes

and monkeys, and even rats (Grill & Norgren, 1978; Steiner, Glaser, Hawilo, & Berridge, 2001).

In our initial experiment we hypothesized that depletion of brain dopamine in rats via a

neurochemical lesion would reduce ‘liking’ reactions for pleasant tastes, based on the notion that

dopamine mediates ‘liking’. We expected this would be reflected as a reduction of hedonic

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orofacial expressions elicited by sweetness. But that is not what we found. We were surprised to

find that liking’ reactions of rats to sugar taste were completely normal even after depletion of

nearly all brain dopamine ‘(Berridge, Venier, & Robinson, 1989). The dopamine lesions did

apparently abolish all motivation – the rats were profoundly aphagic and no longer sought or

consumed food rewards, confirming what others had described. To make sense of these

paradoxical findings, we proposed that mesolimbic dopamine systems mediate ‘wanting’ (in

particular, a psychological process called incentive salience), but not ‘liking’ for the same reward

(Berridge et al., 1989; T. E. Robinson & Berridge, 1993). A follow-up study using implanted

electrodes to stimulate the same mesolimbic systems and raise dopamine levels also failed to

enhance pleasure ‘liking’, despite quadrupling a rat’s ‘wanting’ to eat food rewards (Berridge &

Valenstein, 1991). In humans, similar brain stimulation by many so-called ‘pleasure electrodes’,

upon closer inspection, may also have turned on ‘wanting’ without ‘liking’, and not been so

pleasant after all (Berridge & Kringelbach, 2015).

In the 1990s, it was a lonely scientific position to maintain that dopamine didn’t mediate

pleasure. But in about decade, studies of dopamine in human pleasure began to catch up. For

example, eventually it was reported that suppressing dopamine neurotransmission in people did

not reduce their pleasure ratings of drug rewards, such as cocaine or amphetamine, even when it

reduced their desire to consume more drug (Brauer & De Wit, 1997; M Leyton, Casey, Delaney,

Kolivakis, & Benkelfat, 2005). Similarly, dopamine suppression in ordinary people or in

Parkinson’s disease was reported to not reduce pleasure ratings of tasting delicious foods

(Hardman, Herbert, Brunstrom, Munafo, & Rogers, 2012; Sienkiewicz-Jarosz et al., 2013).

Further, neuroimaging studies began to report that changes in brain dopamine neurotransmission

in people was correlated more with their subjective ratings of wantingdrug and food rewards ,

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than with their liking ratings(Evans et al., 2006; Leyton, 2010; C. T. Smith, Dang, Cowan,

Kessler, & Zald, 2016; Volkow et al., 2002). In sum, many studies have now accumulated

supporting our original conclusion that dopamine mediates desire rather than pleasure (Salamone

& Correa, 2012), and it is now rather rare to find an affective neuroscientist studying reward who

still asserts that dopamine mediates pleasure ‘liking’.

Psychological Features of Incentive Salience: ‘Wanting’

Note that our use of the word ‘wanting’ above is often in quotation marks, because we use that

term to refer to a particular form of desire – namely, mesolimbic incentive salience. This type of

‘wanting’ is often triggered in pulses by reward-related cues or by vivid imagery about the

reward (Berridge, 2012). The ordinary sense of wanting (without quotation marks) refers to a

cognitive desire with a declarative goal. However, incentive salience ‘wanting’ is less connected

to cognitive goals and more tightly linked to reward cues, making those cues attention-grabbing

and attractive (Anderson & Yantis, 2013; Hickey & Peelen, 2015). The cues simultaneously

become able to trigger urges to obtain and consume their rewards (Ostlund, LeBlanc, Kosheleff,

Wassum, & Maidment, 2014; Pecina & Berridge, 2013; Zhou et al., 2011). ‘Wanting’ is

mediated largely by brain mesocorticolimbic systems involving midbrain dopamine projections

to forebrain targets, such as the nucleus accumbens and other parts of striatum (Figure 1). The

intensity of the triggered urge depends both on the cue’s reward association and on the current

state of dopamine-related brain systems in an individual. This interaction allows ‘wanting’ peaks

to be amplified by brain states that heighten dopamine reactivity, such as stress, emotional

excitement, relevant appetites or intoxication (Anselme, 2016; Berridge, 2012; M. J. Robinson &

Berridge, 2013). State-dependent amplification of incentive salience is one reason why many

addicts find it so hard to stop at ‘just one hit’. In the face of an amplified urge, the one hit may

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turn into many hits, or even a lost weekend. It is also a reason why stressful states – or even

happy life stresses like winning the lottery – can promote vulnerability to relapse in addiction

and related disorders (Sinha, 2013). Addiction is not so much about satisfaction, pleasure, need

or withdrawal, by this view, as it is about ‘wanting’.

Ordinarily, cognitive wanting and incentive salience ‘wanting’ go together, so that incentive

salience can give heightened urgency to feelings of cognitive desire. But the two forms of

wanting vs. ‘wanting’ can sometimes dissociate, so that incentive salience can occur either in

opposition to a cognitive desire or even unconsciously in absence of any cognitive desire.

Incentive salience ‘wanting’ in opposition to cognitive wanting, for example, occurs when a

recovering addict has a genuine cognitive desire to abstain from taking drugs, but still ‘wants’

drugs, so relapses anyway when exposed to drug cues or during vivid imagery about them.

Nonconscious ‘wants’ can be triggered in some circumstances by subliminal stimuli, even

though the person remains unable to report any change in subjective feelings while motivation

increases are revealed in their behavior (Childress et al., 2008; Winkielman, Berridge, &

Wilbarger, 2005).

Motivational Salience in Desire Versus Dread

For readers interested in the psychology of emotion and motivation, we note another intriguing

feature of incentive salience. This is that ‘wanting’ brain mechanisms can also operate in a

different neurobiological mode to generate an active coping form of fear (Berridge &

Kringelbach, 2015). Although fear seems almost the psychological opposite of desire in valence,

fearful salience is generated by the same mesolimbic circuitry as incentive salience. Fearful

salience also makes percepts become attention-riveting, but with a negative threatening aspect

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rather than positive attraction, calling out active coping responses (Richard & Berridge, 2011).

This dopamine-related fearful salience has been suggested to contribute to human paranoia

symptoms in schizophrenia (Barch, Treadway, & Schoen, 2014; Heinz & Schlagenhauf, 2010;

Howes & Kapur, 2009) and in psychostimulant-induced psychosis (Cicero, Docherty, Becker,

Martin, & Kerns, 2014).

So Where Does ‘Liking’ Come From in the Brain?

In contrast to the large and robust ‘wanting’ system in the brain, a much smaller and

functionally fragile system appears to generate intense pleasure or ‘liking’ reactions.

Experiments in the Berridge lab have established that this ‘liking’ system comprises a collection

of interactive hedonic hotspots, and this hedonic circuitry may be shared by diverse pleasures

ranging from sensory food and drug pleasures to human cultural and social pleasures (Berridge

& Kringelbach, 2015). The pleasure-generating hotspots are anatomically tiny, neurochemically

restricted, and easily disrupted – perhaps a reason why intense pleasures are relatively few and

far between in life compared to intense desires (Castro & Berridge, 2014; Mahler, Smith, &

Berridge, 2007; Peciña & Berridge, 2005; K. S. Smith, Berridge, & Aldridge, 2011). Each

hedonic hotspot is nestled within its larger limbic structure. For example, a nucleus accumbens

hedonic hotspot is only one cubic millimeter in a rat brain, and probably about a cubic centimeter

in humans. The hotspot constitutes only 10% of total nucleus accumbens volume: the remaining

90% of the nucleus accumbens lacks any ability to enhance ‘liking’, though still robustly causes

intense ‘wanting’.

Hedonic hotspots exist in limbic prefrontal cortex, in orbitofrontal and insula regions, where

they may correspond to human sites that code sensory and higher pleasures (Kringelbach, 2010;

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Kringelbach, O'Doherty, Rolls, & Andrews, 2003; Small, Zatorre, Dagher, Evans, & Jones-

Gotman, 2001). Other hotspots are buried deeper in subcortical brain structures. Each hedonic

hotspot has the special ability when neurochemically stimulated, such as by opioid or

endocannabinoid neurotransmitters (the brain’s natural heroin-like and marijuana-like signals), to

amplify ‘liking’ reactions, and so make sweetness appear even more enjoyable. Dopamine

stimulations even in hedonic hotspots, by contrast always fail to enhance ‘liking’ (K. C. Berridge

& Kringelbach, 2015; K. S. Smith et al., 2011) – the role of dopamine seems restricted to

‘wanting’.

Especially crucial to the normal capacity for pleasure may be a particular hedonic hotspot

located in the ventral pallidum, which lies at the base of the subcortical forebrain (K. S. Smith &

Berridge, 2007). In addition to enhancing ‘liking’ for intense pleasure, this ventral pallidal

hotspot is the only known site in the brain where a small lesion conversely also eliminates

normal pleasure, and reverses the hedonic impact of sweet sensation from ‘liked’ to instead

‘disgusting’ (so that afterwards sucrose elicits bitterness-typical gapes and related negative

expressions) (Berridge & Kringelbach, 2015; Ho & Berridge, 2014).

Addiction Distorts ‘Wanting’ Versus ‘Liking’

Our discovery that ‘wanting’ and ‘liking’ are mediated by dissociable brain systems took us

halfway toward the Incentive-Sensitization theory of addiction (T. E. Robinson & Berridge,

1993, 2008). The other half of the journey came from the discovery around the same time that

brain dopamine systems can be enduringly ‘sensitized’ by many drugs of abuse (cocaine,

amphetamine, heroin, alcohol, nicotine, etc.), not just stimulated while those drugs are actually

on board (T. E. Robinson & Becker, 1986). Mesolimbic sensitization happens especially if the

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drugs are taken repeatedly, and at high doses spaced apart (for example, in weekend binges)

(Kalivas & Stewart, 1991; Post, 1980; T. E. Robinson & Becker, 1986). Once induced,

sensitization is very long lasting, and possibly even permanent.

Early research on sensitization in the T.E. Robinson lab focused particularly on dopamine

neurons, and increases in release of dopamine, but it is now clear that mesolimbic sensitization

changes other neurotransmitters and neurons too. For example, drug sensitization also alters

glutamate neurons that project from cortex to nucleus accumbens (Wolf, 2010), which interact

with dopamine there, and similarly are receiving attention as potential targets of future addiction

therapies (e.g.Creed, Pascoli, & Lüscher, 2015; Douglas & Peter, 2015). Sensitization also

changes the physical structure of mesolimbic neurons, such as altering the shape and number of

tiny spines on dendrites of neurons in nucleus accumbens, which act as their ‘receiving antennae’

for incoming signals (T. E. Robinson & Kolb, 2004; Singer et al., 2009; Steketee & Kalivas,

2011). Initially, the main experimental evidence for mesolimbic sensitization by drugs came

from studies in rodents, but now sensitization is well-documented in humans as well (Boileau et

al., 2007; Paulson & Robinson, 1995; M. J. F. Robinson, Fischer, Ahuja, Lesser, & Maniates,

2015; Vezina & Leyton, 2009).

Functionally, mesolimbic sensitization renders brain ‘wanting’ systems hyper-reactive to

drug cues and contexts, thus conferring more intense incentive salience on those cues or

contexts. Consequently, addicts have stronger cue-triggered urges and intensely ‘want’ to take

drugs (Figure 1). ‘Liking’, by contrast, need not increase with sensitization, and may even

decrease. Sensitized ‘wanting’ can persist for years, even if the person cognitively doesn’t want

to take drugs, doesn’t expect the drugs to be very pleasant, and even long after withdrawal

symptoms have subsided (Berridge & Robinson, 2011; T. E. Robinson & Berridge, 2003; T. E.

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Robinson & Berridge, 2008). Thus, the central tenet of the incentive-sensitization theory is that

addiction becomes compulsive when mesolimbic systems become sensitized and hyper-reactive

to the incentive motivational properties of drug cues (Childress et al., 2008; Ostlund et al., 2014;

Witteman et al., 2015; Zhou et al., 2011). This theory of addiction is specifically meant to

explain individuals who have near-compulsive levels of urge to take drugs, and who remain

vulnerable to a persisting risk of relapse even after a significant period of drug abstinence.

A sensitized dopamine system is not always hyper-active, but it is hyper-reactive to drug

cues and contexts. That hyper-reactivity produces pulses of heightened dopamine release, brain

activations and motivation that last seconds or minutes (T. E. Robinson & Berridge, 2008;

Tindell, Berridge, Zhang, Peciña, & Aldridge, 2005). Drug contexts powerfully gate the ability

of both drugs themselves and of discrete cues to elicit sensitized neural hyper-reactivity (M.

Leyton & Vezina, 2013; T. E. Robinson, Browman, Crombag, & Badiani, 1998). This means

that surges of intense ‘wanting’ are most likely to be triggered when drug cues are encountered

(or imagined) in contexts previously associated with taking drugs.

Sensitization in Human Addiction

Laboratory neuroimaging studies have shown that even the oral administration of relatively

low doses of amphetamine can produce mesolimbic sensitization in people without a history of

drug use (Boileau et al., 2006; Leyton & Vezina, 2013). Furthermore, in nondependent cocaine

users the ability of self-administered cocaine (taken by the intranasal route) to increase dopamine

levels in the ventral striatum is positively correlated with amount of lifetime cocaine use,

suggesting past use sensitized dopamine systems (Cox et al., 2009). However, there is reason to

expect even stronger sensitization from higher street-typical doses, or by intravenous or smoking

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routes of consumption (which deliver drugs to the brain more rapidly than swallowing or

snorting), based on animal studies (Allain, Minogianis, Roberts, & Samaha, 2015). Indeed,

addicts tend to prefer to smoke or inject drugs, because those routes deliver drugs to the brain

more rapidly. Consequently, real-life addicts may have greater mesolimbic sensitization than so

far demonstrated by laboratory studies in nonusers.

Do human addicts actually show the brain hyper-reactivity to drug cues that is posited by

incentive-sensitization? The short answer is ‘yes’. There have been many reports over the past

10 years that mesolimbic brain responses to drug cues, such as viewing photos of drug

paraphernalia or of other people taking drugs, are enhanced in individuals with addiction (Kühn

& Gallinat, 2011). Furthermore, “more years of cocaine use [are] associated with greater

activation to cocaine cues in ventral striatum” (Prisciandaro et al., 2014), indicating

progressively intense sensitization. Similar findings have been reported with alcohol use (Claus,

Ewing, Filbey, Sabbineni, & Hutchison, 2011).

We note as a caveat that most reports of such hyper-reactivity used fMRI measures, which

do not directly measure dopamine, but rather oxygenated blood signals (BOLD), which are used

to infer neural activity. However, recent research confirms that dopamine release does cause

striatal BOLD activations (Ferenczi et al., 2016), supporting the interpretation that fMRI hyper-

reactivity to drug cues in addicts reflects a higher dopamine surge, and indicates incentive-

sensitization. Further, several studies that have used more direct PET measures of dopamine

release in people (i.e., via dopamine displacement of radioactive raclopride from D2 receptors)

also confirm that drug cues do trigger higher increases in dopamine release, and in fact, “the

greater the cue-induced dopamine release the greater the craving” to take more drug (Leyton &

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Vezina, 2013, p. 2004). These intense cue-triggered neural signatures are very much what one

would expect based on the incentive-sensitization theory of addiction.

Disentangling Reports of Mesolimbic Suppression Versus Sensitization in Addiction

As another caveat, it is only fair to note that some studies have reported nearly the opposite

of sensitized brain responses as described above: that is, neural suppression or blunted rise in

dopamine displacement elicited when an addict takes a drug. Suppressed brain responses are

typically not to the drug cues that trigger urges, but rather to drugs themselves once actually

taken, such as amphetamine or methylphenidate (Volkow, Koob, & McLellan, 2016). However,

we caution that two points need to be considered before jumping to a conclusion that addicts

have too little brain dopamine, as some have suggested. First, suppression of drug-elicited brain

activation to drugs is by no means a universal finding. For example, as mentioned above,

sensitized or increased dopamine rises elicited by exposure to a drug are also sometimes

reported. For instance, alcohol is reported to elicit greater dopamine release in the striatum of

alcoholics than in social drinkers (Yoder et al., 2016). Still, suppression of drug-induced

dopamine is found often enough in addicts to have led some observers to suggest that the essence

of addiction is primarily too-little dopamine in nucleus accumbens and striatum (Volkow et al.,

2016). That dopamine-deficit suggestion is quite a contrast to incentive-sensitization, and is

often wrapped together implicitly with the older assumption that lower dopamine causes reduced

pleasure and that addicts simply seek pleasure (despite the emerged consensus that the dopamine

pleasure hypothesis not true). Second, however, partial compensations to excessive dopamine

stimulation may occur in the brain after heavy drug use, which at least for a while can mask the

expression of neural sensitization. We would agree that compensatory neural suppressions (e.g.,

receptor downregulation) do accompany heavy drug use, while drug-taking continues.

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Suppressions produce tolerance to drug highs (and to the aversive effects of some addictive

drugs -- which permits the person to take higher doses, inducing even more tolerance). Neural

suppressions also produce withdrawal for a while, once the drug is finally stopped.

However, even the same investigators that report suppression of responses to drugs often

also report the same addicts show intense neural hyper-activations – not suppressions -- to the

drug cues that trigger urges to take drugs. That is, compensatory suppressions of drug-elicited

reactions as consequences of over-stimulation need not contradict incentive-sensitization as the

primary mechanism for the compulsive craving in addiction, consistent with incentive-

sensitization. Further, many tolerance-related neural suppressions are merely temporary.

Suppressions are partial compensatory responses to the high levels of mesolimbic stimulation

induced by drugs, essentially a temporary cellular effort by neurons to turn down their levels of

neurochemical over-stimulation. Sensitization and tolerance can develop simultaneously in the

same brain while drug is being taken, because they have parallel mechanisms involving different

intra-cellular signalling cascades. But many tolerance/withdrawal suppressions are apt to fade

within weeks if drug-taking is stopped. By contrast the neural changes that cause incentive-

sensitization do not fade over months of drug abstinence – if anything, sensitization grows for

some time during abstinence (Paulson & Robinson, 1995), a phenomenon sometimes called

‘incubation of drug craving’, which is an increase in relapse vulnerability after a month or so of

drug abstinence (Pickens et al., 2011). Incubation of craving is impossible to explain by a neural

suppression or withdrawal view of addiction, because those fade, not grow, over a month of

abstinence, but is entirely plausible in light of incentive-sensitization. Finally, suppression of

neural responses to drugs may occur mostly in test situations that are very different from

situations in which drugs were usually taken – such while in a neuroimaging scanner in a

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hospital setting (M. Leyton & Vezina, 2013). By contrast, neural suppression may be converted

into sensitized hyper-reactions when neuroimagers take efforts to provide realistic drug-related

cues and contexts during the neuroimaging test (Leyton & Vezina, 2013). Early animal studies

showed that giving drug in a test environment where it never before was experienced can

completely prevent the expression of behavioral and neural sensitization, even when it clearly

has been induced , whereas a previously drug-associated context enables the sensitized response

to fully reappear again when drug is retaken (T. E. Robinson et al., 1998). That is, sensitized

‘wanting’ urges are much more likely to occur in drug-associated contexts than in biomedical

neuroimaging situations. Recent neuroimaging evidence indicates that drug-related contexts

gate sensitized brain reactions in humans too (Leyton & Vezina, 2013). Therefore, it may be

crucial that PET studies of drug-elicited brain responses take steps to better recreate drug-related

contexts and cues in order to reveal sensitized hyper-reactive brain responses to drugs that would

occur in real-life drug situations, and which may underlie addictive urges to take more drugs. Of

course, how addicts perceive contexts is likely complex, so it might help to let addicts also

actively engage in their drug-taking rituals (e.g., preparing lines of cocaine to sniff, or preparing

an injection), or to experience diverse drug-related auditory, smell, taste or other sensations in

order to unmask sensitized hyper-reactivity in mesolimbic systems (Cox et al., 2009). It might

also be useful to test with the same drug an addict most commonly takes rather than with an

unfamiliar drug (such as methylphenidate, which has been substituted for an addict’s habitual

drug in some neuroimaging studies).

Individual vulnerability. Another important point that any addiction explanation must deal

with is that most people who take drugs never become addicts. For example, only about 30% of

people who take cocaine actually go on to become long-term addicts. Accordingly, individuals

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also differ considerably in their susceptibility to mesolimbic sensitization, even when exposed to

the same drugs and doses (Becker, Perry, & Westenbroek, 2012; Robinson & Berridge, 2008).

Genetic factors are important determinants of susceptibility to sensitization in rodents, and genes

also contribute strongly to addiction vulnerability in humans (Franklin et al., 2011; Hoft, Stitzel,

Hutchison, & Ehringer, 2011; Hutchison et al., 2008; Moeller et al., 2013). Other determinants

of sensitization vulnerability include gender and the presence of sex hormones, and whether the

individual has had major stresses in life before taking drugs (Becker, Perry, & Westenbroek,

2012; T. E. Robinson & Berridge, 2008). Individuals with combinations of these several factors

may be most at risk to develop incentive-sensitization and addiction. Finally, among those who

experiment with drugs in the first place, important situational factors can facilitate incentive-

sensitization, or alternatively make it less likely. These include how long drugs have been taken,

whether dose has escalated, and whether the person took drugs by routes that resulted in drug

rapidly reaching the brain (i.e., inhalation or intravenous use).

Another type of individual difference concerns neuropsychological traits of incentive

salience that might predispose toward either drug taking or addiction. For example, even

animals differ as individuals in their propensity to attribute incentive salience to discrete

predictive reward cues (T. E. Robinson, Yager, Cogan, & Saunders, 2014). For example, some

rats come to rapidly approach a discrete Pavlovian cue that predicts delivery of a food or drug

reward (such as sudden appearance of a lever), and will work avidly to get the cue (these

individuals are called sign-trackers). However, other rats will instead go directly to the location

of impending delivery of a food reward when its predictive cue appears (called goal-trackers).

Studies in the T.E. Robinson lab have found that discrete cocaine or opioid cues acquire greater

incentive salience in sign-trackers than in goal-trackers, and in some situations sign-trackers are

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also more likely than goal-trackers to show cue-triggered relapse of drug-taking behavior (T. E.

Robinson et al., 2014). However, both types of individuals eventually show addictive-type

patterns of high drug intake when they have weeks of intermittent access to cocaine, in binge-

like periods, and develop robust incentive-sensitization(Kawa, Bentzley, & Robinson, 2016).

Thus, being relatively attracted to discrete reward cues may make some individuals more

susceptible to develop addiction when they initially start to use drugs (Mahler & de Wit, 2010;

van Hemel-Ruiter, de Jong, Ostafin, & Oldehinkel, 2015; Vollstädt-Klein et al., 2012), though

most individuals may develop neural incentive-sensitization eventually if they take drugs for

long enough and at high enough doses.

Is incentive-sensitization a brain disease? Addiction has sometimes been called a ‘brain

disease’ (Leshner, 1997). Yet recently that label has come under criticism on the grounds that

some addicts may not regard themselves as diseased, incentives often still can influence drug use

as though it were an ordinary choice, and because believing that one has a ‘brain disease’ could

encourage a fatalistic acceptance of the condition (Hall, Carter, & Forlini, 2015; Lewis, 2015).

Also, though addiction is accompanied by distinct changes in the brain, some critics also note

that related changes in the brain can occur in normal life: indeed, the brain mechanisms of

addiction do overlap the mechanisms of ordinary desires such as love or hunger that are shared

by everyone.

While these objections have some validity, we do believe that incentive-sensitization can

make the temptations faced by addicts harder to resist than those most other people are called

upon to face. This is because the underlying neural sensitization can distort psychological

incentive salience function to a pathological degree, with deleterious consequences. If success

versus failure is probabilistic when temptations are very strong, and if success in escaping

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addiction requires saying no every time a temptation occurs, then a dopamine-sensitized person

who faces a series of hundreds of intense temptations may eventually be expected to fail. Such

features may make the ‘brain disease’ label a reasonably fair description.

Other Behavioral Addictions?

Various ‘behavioral addictions’ have emerged in recent years that do not involve drugs at

all: eating addiction, gambling addiction, sex or pornography addiction, internet addiction,

shopping addiction, and so on (Davis & Carter, 2009; Gearhardt et al., 2011; Hartston, 2012;

Linnet et al., 2012; S. S. O'Sullivan et al., 2011; Ray et al., 2012; Voon et al., 2014). Although

drugs were central to mechanisms underlying the original incentive-sensitization hypothesis,

perhaps surprisingly, neural sensitization of ‘wanting’ mechanisms may in some cases occur

without drugs. In support, evidence is emerging that individuals with these behavioral addictions

may have some sensitization-like patterns of brain hyper-reactivity to cues related to their own

personal addictions (Davis & Carter, 2009; Gearhardt et al., 2011; Hartston, 2012; Linnet et al.,

2012; O'Sullivan et al., 2011; Ray et al., 2012; Voon et al., 2014). Conceivably, sensitization-

related brain changes arise in some highly susceptible individuals to produce these addictions

without need of drugs, through mechanisms not yet understood.

Related proof-of-principle evidence for the idea that diverse compulsive motivations such as

gambling can be caused by hyper-stimulation of dopamine-related systems also comes from

Parkinson’s patients, about 15% of whom develop what is called dopamine dysregulation

syndrome when treated with newer dopamine-stimulating medications that directly activate their

brain dopamine receptors (i.e., direct agonist medications) (Callesen, Scheel-Kruger,

Kringelbach, & Moller, 2013; Friedman & Chang, 2013; Ondo & Lai, 2008; Politis et al., 2013).

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These patients can develop intense compulsive motivations to pursue gambling, shopping, sex,

internet use, excessive hobbies, or similar activities (O'Sullivan, Evans, & Lees, 2009). Some

patients may even take excessive amounts of their medication in a more classic drug-addiction

fashion. Usually, the compulsive motivations rapidly fade if the dopamine-stimulating

medications are stopped. This pattern demonstrates intense and idiosyncratically diverse ‘wants’

arising from dopamine-stimulating medications, and is also a further contradiction of the notion

that dopamine-suppression causes addictions (i.e., since Parkinson’s patients are in dopamine

suppression states prior to medication or if taken-off medication, but no longer have compulsive

motivations at those times). It provides further support for the sensitization idea that dopamine

over-stimulation is the more likely culprit behind addictive compulsions (i.e., while taking high

doses of medications that stimulate dopamine receptors). Finally, such patients with intense

motivations have virtually never been reported to experience intense pleasure from their

medications or compulsions, any more than individuals with spontaneous behavioral addictions –

or some drug addicts (Pettorruso et al., 2016). In short, evidence continues to build that

dopamine hyper-reactivity produces intense reward ‘wanting’ but not ‘liking’, and can cause

addictions.

Treatment Implications

At present, most addiction medications are of quite limited efficacy. Opioid blockers (e.g.,

naltrexone) conceivably help somewhat blunt ‘wanting’ as well ‘liking’ peaks. Anti-depressants

take the edge off negative mood-based reasons to take drugs again, and opioid-substitutes

prevent withdrawal symptoms. Immune-based vaccines help reduce drug-induced highs, though

can be circumvented by taking higher doses or different drugs. Psychological approaches, such

as cognitive and behavioral therapies, 12-step programs, contingency management and

Liking, Wanting and Addiction

19

mindfulness therapy arguably remain more effective than any medications available today. Still,

while those psychological approaches are quite useful in helping some individuals to escape

addiction, they are still not sufficient for many others.

We suggest that a more effective neurobiological treatment would need to reverse the

neuroadaptations underlying sensitized mesolimbic hyper-reactivity to drug cues, yet not impede

normal motivations nor induce adverse side effects. In practice this may be difficult to achieve,

though in principle not impossible. Encouragingly, some recent findings from animal studies

have suggested it may be possible to rather specifically reverse sensitized mesolimbic hyper-

reactivity by new neurobiological techniques, without adverse other effects (Creed et al., 2015).

Although human applications are still a long way off, such findings give at least some reason to

hope that more effective sensitization-reversing treatments might be developed in future.

Conclusion

In summary, a quarter-century after we proposed the Incentive-Sensitization theory of

addiction, we conclude that its key tenets still seem well supported. In addicts mesolimbic

circuits are hyper-responsive to drug cues, which may cause strong cue-triggered ‘wanting’ to

take drugs, leading to relapse. Our journey into understanding addiction began with basic

science investigations of brain systems and their psychological functions in animals. The

insights from those studies have proven remarkably applicable to humans. Those insights were

that the psychological process of motivationally ‘wanting’ a reward has distinct brain

mechanisms from hedonically ‘liking’ the same reward, and that sensitization of dopamine-

related hyper-reactivity specifically promotes excessive ‘wanting’. Gradually, substantial

evidence from both human and animal studies has emerged to further support and refine those

Liking, Wanting and Addiction

20

conclusions. Finally, the scope of clinical applications has extended in the past decade beyond

drug addiction to other behavioral addictions, schizophrenia, depression, Parkinson’s disease,

and other forms of psychopathology. This story is still being written, and it seems likely that

future findings will continue to reveal exciting facets of normal reward processes in the brain,

how their distortion can impact psychological disorders, and how new therapies might someday

overcome distortions to improve function again.

Liking, Wanting and Addiction

21

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Figure 1. ‘Liking’ and ‘wanting’ in brain and in addiction. ‘Wanting’ is mediated by a robust brain

system including dopamine projections (left, dark gray), whereas ‘liking’ is mediated by a restricted brain

system of small hedonic hotspots (white) (described in Berridge & Kringelbach, 2015). The incentive-

sensitization theory of addiction (right) shows how ‘wanting’ may grow over time independently of

‘liking’ as an individual becomes an addict, due to sensitization of brain mesolimbic systems. (The figure

was adapted by Shannon Cole and Daniel Castro from Robinson & Berridge, 1993).

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Author’s and Editor’s Notes

Editor’s note. The authors received the 2016 APA Award for Distinguished Scientific

Contribution for collaboration. This article is based on an invited presentation at the 124th

Annual Convention of the American Psychological Association, held August 4–7, 2016, in

Denver, Colorado.

Author’s note. Kent C. Berridge and Terry E. Robinson, Department of Psychology, University of

Michigan.

We thank Shannon Cole and Daniel Castro for redrawing Figure 1. Our research has been supported

by grants from the National Institutes of Health (DA015188 and MH63649 to Kent Berridge and PO1

DA031656 to Terry E. Robinson).

Correspondence concerning this article should be addressed to Kent C. Berridge, Department of

Psychology, University of Michigan, 530 Church Street, Ann Arbor, MI 48109-1043. Email:

[email protected] or [email protected]