Scientists Identify Key Brain Circuits that Control Compulsive Drinking in Rats

Gallo Center Research Could Have Direct Application For Treating Human Drinking Problems

A research team led by scientists from the Ernest Gallo Clinic and Research Center at UC San Francisco has identified circuitry in the brain that drives compulsive drinking in rats, and likely plays a similar role in humans.

The scientists found they could reduce compulsive drinking in rats by inhibiting key neural pathways that run between the prefrontal cortex, which is involved with higher functions such as critical thinking and risk assessment, and the nucleus accumbens, a critical area for reward and motivation.

The authors noted that there are already several FDA-approved medications that target activity in these pathways, thus potentially opening an accelerated track to new treatments for compulsive drinking.

The study describing their finding was published online on June 30 in Nature Neuroscience.

The study was conducted on rats that regularly drank 20 percent alcohol. The rats drank both unmixed alcohol and alcohol mixed with extremely bitter quinine, said senior investigator F. Woodward Hopf, PhD, an assistant adjunct professor of neurology at UCSF.

Hopf explained that this alcohol-quinine solution, which he described as “like a vodka tonic without the sugar,” is often used as a rodent model of compulsive drinking, or “drinking in the face of negative consequences.” In rats, he said, the negative consequence is the bitter taste, while in humans who drink compulsively, “the negative consequences are profound: people continue to drink despite the potential loss of jobs, marriages, freedom, even their lives.”

The drinking rats showed a notable increase in the NMDA receptor (NMDAR), which lead author Taban Seif, PhD, a Gallo Center researcher, called “a molecule that excites the brain.” When the rats were injected with an NMDAR blocker, their consumption of quinine-laced alcohol dropped significantly, while regular alcohol use was unaffected. “In other words, only the compulsive drinking was affected,” said Seif.

Focus on Two Regions of the Prefrontal Cortex

The team then focused its research on connections from two specific regions of the rats’ prefrontal cortex where they had discovered the presence of unusual types of NMDARs: the medial prefrontal cortex, which mediates conflict during decision-making, and the insula, which is critical for self-awareness and feelings.

“In a non-addict, these brain areas tell you when something is potentially harmful and bad, and to run away as fast as possible,” said Hopf. “But if you’re a compulsive drinker, it seems instead that they give you a comforting pat on the back, in effect telling you it’s OK to have another drink, nothing to worry about.”

Using a technique called optogenetics, the scientists inserted halorhodopsin, a light-sensitive protein, into these areas. They then used fiber-optic cables implanted in the rats’ brains to send pulses of laser light that activated the halorhodopsin, which in turn inhibited the regions’ connections to the nucleus accumbens. The researchers found that rats inhibited in this way drank significantly less quinine-laced alcohol, while their intake of regular alcohol solution remained unaffected.

“The fact that we reduced the rats’ compulsive drinking using two different methods – an NMDAR blocker and direct inhibition of connections – tells us that we have probably identified the right areas,” said Hopf.

Potential Treatments for Humans

The next logical step for the research team, said Hopf, would be to work with clinical researchers on an NMDAR blocker trial in human subjects.

“What is interesting is that we have a new drug which could perhaps treat compulsive aspects of drinking,” said Hopf, “but only if you are in conflict about your drinking – if you care. Any therapy with NMDAR blockers would need a strong behavioral and cognitive component to make sure the patient stayed mentally engaged.”

Seif and Hopf also plan further experimental studies focusing on how the insula drives behavior and connects to other areas of the brain.

Voices may not trigger brain’s reward centers in children with autism

In autism, brain regions tailored to respond to voices are poorly connected to reward-processing circuits, according to a new study by scientists at the Stanford University School of Medicine.

The research could help explain why children with autism struggle to grasp the social and emotional aspects of human speech. “Weak brain connectivity may impede children with autism from experiencing speech as pleasurable,” said Vinod Menon, PhD, senior author of the study, published online June 17 in Proceedings of the National Academy of Sciences. Menon is a professor of psychiatry and behavioral sciences at Stanford and a member of the Child Health Research Institute at Lucile Packard Children’s Hospital.

"The human voice is a very important sound; it not only conveys meaning but also provides critical emotional information to a child," said Daniel Abrams, PhD, a postdoctoral scholar in psychiatry and behavioral sciences who was the study’s lead author. Insensitivity to the human voice is a hallmark of autism, Abrams said, adding, "We are the first to show that this insensitivity may originate from impaired reward circuitry in the brain."

The study focused on children with a high-functioning form of autism. They had IQ scores in the normal range and could speak and read, but had difficulty holding a back-and-forth conversation or understanding emotional cues in another person’s voice.

The scientists compared functional magnetic resonance imaging brain scans from 20 of these children with scans from 19 typically developing children, paying particular attention to a portion of the brain that responds selectively to the sound of human voices. Prior research has shown that adults with autism had low voice-selective cortex activity in response to speech. But until this study by Menon and his colleagues, no one had looked at connections between the voice-selective cortex and other brain regions in individuals with autism.

The new study found that in children with a high-functioning form of autism, the voice-selective cortex on the left side of the brain was weakly connected to the nucleus accumbens and the ventral tegmental area — brain structures that release dopamine in response to rewards. The voice-selective cortex on the right side of the brain, which specializes in detecting vocal cues such as intonation and pitch, was weakly connected to the amygdala, which processes emotional cues.

The weaker these connections in children with autism, the worse their communication deficits, the study showed. The researchers were able to predict the children’s scores on the verbal portion of a standard test of autism severity by looking at the degree of impairment in these brain connections.

The findings may help to validate some autism therapies already in use, said co-author Jennifer Phillips, PhD, a clinical associate professor of psychiatry and behavioral sciences at Stanford who also treats children with autism at Packard Children’s. For instance, pivotal-response training aims to increase social use of language in children who can speak some words but who usually do not talk to others.

"Pivotal-response training goes after ways to naturally motivate kids to start using language and other forms of social interaction," Phillips said. Future studies could test whether brain connections leading from voice to reward centers are strengthened by autism therapies, she added.

The findings also help resolve a long-standing debate about why individuals with autism show less-than-normal interest in human voices. The team investigated two competing theories to explain the phenomenon: that individuals with autism have a deficit in their social motivation, or, alternatively, that they have sensory-processing deficits which impair their ability to fully hear human voices. The new study found normal connections between voice-selective cortex and primary auditory brain regions in children with high-functioning autism, suggesting that these children do not have sensory-processing deficits.

The next steps for researchers include studying the consequences of the weak voice-to-reward circuit in autism. “It is likely that children with autism don’t attend to voices because they are not rewarding or emotionally interesting, impacting the development of their language and social communication skills,” Menon said. “We have discovered an aberrant brain circuit underlying a core deficit in autism; our findings may aid the development of new treatments for this disorder.”

(Image: Getty Images)

Researchers focus on a brain protein and an antibiotic to block cocaine craving

A new study conducted by a team of Indiana University neuroscientists demonstrates that GLT1, a protein that clears glutamate from the brain, plays a critical role in the craving for cocaine that develops after only several days of cocaine use.

The study, appearing in The Journal of Neuroscience, showed that when rats taking large doses of cocaine are withdrawn from the drug, the production of GLT1 in the nucleus accumbens, a region of the brain implicated in motivation, begins to decrease. But if the rats receive ceftriaxone, an antibiotic used to treat meningitis, GLT1 production increases during the withdrawal period and decreases cocaine craving.

George Rebec, professor in the Department of Psychological and Brain Sciences, said drug craving depends on the release of glutamate, a neurotransmitter involved in motivated behavior. Glutamate is released in response to the cues associated with drug taking, so when addicts are exposed to these cues, their drug craving increases even if they have been away from the drug for some time.

The same behavior can be modeled in rats. When rats, who self-administer cocaine by pressing a lever that delivers the cocaine into their bodies, are withdrawn from the drug for several weeks, their craving returns if they are exposed to the cues that accompanied drug delivery in the past; in this case, a tone and light. But if the rats are treated with ceftriaxone during withdrawal, they no longer seek cocaine when the cues are presented.

Ceftriaxone appears to block craving by reversing the decrease in GLT1 caused by repeated exposure to cocaine. In fact, ceftriaxone increases GLT1, which allows glutamate to be cleared quickly from the brain. The Rebec research group localized this effect to the nucleus accumbens by showing that if GLT1 was blocked in this brain region even after ceftriaxone treatment, the rats would relapse.

While an earlier paper of Rebec’s group showed the effects of ceftriaxone on cocaine craving, the new paper was the first to localize the effects of ceftriaxone to the nucleus accumbens and was the first to show that ceftriaxone works after long withdrawal periods.

"The idea is that increasing GLT1 will prevent relapse. If we block GLT1, the ceftriaxone should not work," Rebec said. "We now have good evidence that ceftriaxone is acting on GLT1 and that the nucleus accumbens is the critical site."

Rebec said prior work on Huntington’s disease, a neurodegenerative disorder, alerted him and his team to the way ceftriaxone acts on the expression of GLT1, a protein that removes glutamate from the brain. Glutamate removal is a problem in Huntington’s disease, and Rebec’s team found that ceftriaxone increases GLT1 and improves neurological signs of the disease in mouse models.

It now is important to determine why cocaine decreases GLT1 and to see whether other drugs of abuse have the same effect. Rebec and colleagues have shown that ceftriaxone also can decrease the craving for alcohol in rats selectively bred to prefer alcohol.

Drug cues are one factor that can trigger relapse. Future work also will examine whether ceftriaxone can block drug craving induced by stress or by re-exposure to the drug. If so, it would mean that GLT1 could become an important target in the search for treatments to prevent drug relapse. Now, Rebec said, there are a number of factors to study. “We don’t yet know how long the effects of ceftriaxone last. Does an addict have to be on it for a month or will it lose its effectiveness? We don’t yet know what will happen.”

In the cocaine study, the rats self-administer cocaine for six hours a day for up to 11 days. Their behavior is much like that of a human addict.

"You might think that because they’re in there, they just take more, but they don’t just take more," Rebec said. "Like human addicts, they take the drug more and more rapidly and they want to get to it more and more quickly."

Withdrawal serves as an incubation period during which craving increases if it is activated by cues or other factors. “Something changes in the brain during that time to trigger the craving or make it more likely that you want the drug,” Rebec said. “That’s what ceftriaxone seems to be interfering with.”

Ceftriaxone is now in clinical trials on people with ALS, also known as Lou Gehrig’s disease, which has many mechanisms in common with other neurodegenerative diseases such as Huntington’s disease and Alzheimer’s.

Researchers identify pathway that may protect against cocaine addiction

A study by researchers at the National Institutes of Health gives insight into changes in the reward circuitry of the brain that may provide resistance against cocaine addiction. Scientists found that strengthening signaling along a neural pathway that runs through the nucleus accumbens — a region of the brain involved in motivation, pleasure, and addiction — can reduce cocaine-seeking behavior in mice.

Research suggests that about 1 in 5 people who use cocaine will become addicted, but it remains unclear why certain people are more vulnerable to drug addiction than others.

“A key step in understanding addiction and advancing treatment is to identify the differences in brain connectivity between subjects that compulsively take cocaine and those who do not,” said Ken Warren, Ph.D., acting director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Researchers at NIAAA, part of NIH, conducted the study.

“Until now, most efforts have focused on finding traits associated with vulnerability to develop compulsive cocaine use. However, identifying mechanisms that promote resilience may prove to have more therapeutic value,” said the paper’s senior author, Veronica Alvarez, Ph.D., acting chief of the Section on Neuronal Structure in the NIAAA Laboratory for Integrative Neuroscience. The study is available on the Nature Neuroscience website ahead of print.

In the study, mice were conditioned to receive an intravenous dose of cocaine each time they poked their nose into a hole in their enclosure. Cocaine was then made unavailable for periods of time during the day. Some of the mice would stop seeking the drug once it was removed while others would obsessively continue to poke the hole in an effort to obtain the drug.

Mice that quickly stopped seeking the drug were found to have stronger connections along the indirect pathway — a neural tract that forms indirect projections into the midbrain and contains cells called medium spiny neurons expressing dopamine D2 receptors (D2-MSNs). A parallel pathway — known as the direct pathway — forms direct projections into the midbrain neurons and contains medium spiny neurons expressing D1 receptors (D1-MSNs). These two pathways are thought to work together in complementary but sometimes opposing ways to affect behavior.

"We were very surprised by the results of the study because we were originally looking for vulnerability factors for developing compulsive drug use,” said Dr. Alvarez. “Instead, we found changes that only happened in subjects that show a resilience to becoming compulsive drug users. Resilient mice had a strong inhibitory circuit that allowed them to exert better control over their drug intake."

To test this observation, researchers used lasers to activate individual neurons, and found that stimulating D2-MSNs in the nucleus accumbens decreased cocaine seeking in the mice. Blocking D2-MSN signaling with a chemical process increased motivation to obtain cocaine.

“This research advances our understanding of how the recruitment, activation and the interaction among brain circuits can either restrain or increase motivation to take drugs,” said David Shurtleff, Ph.D. acting deputy director of the National Institute on Drug Abuse.

Previous studies have shown that people with lower levels of dopamine D2 receptors in the striatum, a brain region associated with reward and working memory, are more likely to develop compulsive behaviors toward stimulant drugs.

Dopamine is a key neurotransmitter involved in reward-based learning and addiction. Cocaine disrupts communication between neurons at the synapse, the small junction between nerve cells, by blocking the reabsorption of dopamine into the transmitting neuron. As a result, dopamine continues to stimulate the receiving neuron, causing feelings of alertness and euphoria.

Why we buy music

New study shows what happens in the brain to make music rewarding

A new study reveals what happens in our brain when we decide to purchase a piece of music when we hear it for the first time. The study, conducted at the Montreal Neurological Institute and Hospital – The Neuro, McGill University and published in the journal Science on April 12, pinpoints the specific brain activity that makes new music rewarding and predicts the decision to purchase music.

Participants in the study listened to 60 previously unheard music excerpts while undergoing functional resonance imaging (fMRI) scanning, providing bids of how much they were willing to spend for each item in an auction paradigm. “When people listen to a piece of music they have never heard before, activity in one brain region can reliably and consistently predict whether they will like or buy it, this is the nucleus accumbens which is involved in forming expectations that may be rewarding,” says lead investigator Dr. Valorie Salimpoor, who conducted the research in Dr. Robert Zatorre’s lab at The Neuro and is now at Baycrest Health Sciences’ Rotman Research Institute. “What makes music so emotionally powerful is the creation of expectations. Activity in the nucleus accumbens is an indicator that expectations were met or surpassed, and in our study we found that the more activity we see in this brain area while people are listening to music, the more money they are willing to spend.”

The second important finding is that the nucleus accumbens doesn’t work alone, but interacts with the auditory cortex, an area of the brain that stores information about the sounds and music we have been exposed to. The more a given piece was rewarding, the greater the cross-talk between these regions. Similar interactions were also seen between the nucleus accumbens and other brain areas, involved in high-level sequencing, complex pattern recognition and areas involved in assigning emotional and reward value to stimuli.  

In other words, the brain assigns value to music through the interaction of ancient dopaminergic reward circuitry, involved in reinforcing behaviours that are absolutely necessary for our survival such as eating and sex, with some of the most evolved regions of the brain, involved in advanced cognitive processes that are unique to humans.

“This is interesting because music consists of a series of sounds that when considered alone have no inherent value, but when arranged together through patterns over time can act as a reward, says Dr. Robert Zatorre, researcher at The Neuro and co-director of the International Laboratory for Brain, Music and Sound Research. “The integrated activity of brain circuits involved in pattern recognition, prediction, and emotion allow us to experience music as an aesthetic or intellectual reward.”

“The brain activity in each participant was the same when they were listening to music that they ended up purchasing, although the pieces they chose to buy were all different,” adds Dr. Salimpoor. “These results help us to see why people like different music – each person has their own uniquely shaped auditory cortex, which is formed based on all the sounds and music heard throughout our lives. Also, the sound templates we store are likely to have previous emotional associations.”

An innovative aspect of this study is how closely it mimics real-life music-listening experiences.  Researchers used a similar interface and prices as iTunes. To replicate a real life scenario as much as possible and to assess reward value objectively, individuals could purchase music with their own money, as an indication that they wanted to hear it again. Since musical preferences are influenced by past associations, only novel music excerpts were selected (to minimize explicit predictions) using music recommendation software (such as Pandora, Last.fm) to reflect individual preferences.

The interactions between nucleus accumbens and the auditory cortex suggest that we create expectations of how musical sounds should unfold based on what is learned and stored in our auditory cortex, and our emotions result from the violation or fulfillment of these expectations. We are constantly making reward-related predictions to survive, and this study provides neurobiological evidence that we also make predictions when listening to an abstract stimulus, music, even if we have never heard the music before. Pattern recognition and prediction of an otherwise simple set of stimuli, when arranged together become so powerful as to make us happy or bring us to tears, as well as communicate and experience some of the most intense, complex emotions and thoughts.

(Image: Peter Finnie and Ben Beheshti)

Discovery could yield treatment for cocaine addicts

Scientists have discovered a molecular process in the brain triggered by cocaine use that could provide a target for treatments to prevent or reverse addiction to the drug.

Reporting in the Journal of Neuroscience, Michigan State University (MSU) neuroscientist A.J. Robison and colleagues say cocaine alters the nucleus accumbens, the brain’s pleasure center that responds to stimuli such as food, sex and drugs.

“Understanding what happens molecularly to this brain region during long-term exposure to drugs might give us insight into how addiction occurs,” said Robison, assistant professor in the Department of Physiology and in the Neuroscience Program.

The researchers found that cocaine causes cells in the nucleus accumbens to boost production of two proteins, one associated with addiction and the other related to learning. The proteins have a reciprocal relationship – they increase each other’s production and stability in the cells – so the result is a snowball effect that Robison calls a feed-forward loop.

Robison and colleagues demonstrated that loop’s essential role in cocaine responses by manipulating the process in rodents. They found that raising production of the protein linked to addiction made animals behave as if they were exposed to cocaine even when they weren’t. They also were able to break the loop, disrupting rodents’ response to cocaine by preventing the function of the learning protein.

“At every level that we study, interrupting this loop disrupts the process that seems to occur with long-term exposure to drugs,” said Robison, who conducted the study as a postdoctoral fellow at Mount Sinai School of Medicine in New York City before joining the faculty at MSU.

Robison said the study was particularly compelling because it found signs of the same feed-forward loop in the brains of people who died while addicted to cocaine.

“The increased production of these proteins that we found in the animals exposed to drugs was exactly paralleled in a population of human cocaine addicts,” he said. “That makes us believe that the further experiments and manipulations we did in the animals are directly relevant to humans.”

Robison said the growing understanding of addiction at the molecular level could help pave the way for new treatments for addicts.

“This sort of molecular pathway could be interrupted using genetic medicine, which is what we did with the mice,” he said. “Many researchers think that is the future of medicine.”

(Image: UTHSC)

Stanford psychologists uncover brain-imaging inaccuracies

Pictures of brain regions “activating” are by now a familiar accompaniment to any neurological news story. With functional magnetic resonance imaging, or fMRI, you can see specific brain regions light up, standing out against the background like night owls’ apartment windows.

It’s easy to forget that these brain images aren’t real snapshots of brain activity. Instead, each picture is the result of many layers of analysis and interpretation, far removed from raw data.

"It’s just one representation of brain activity," said Matthew Sacchet, a PhD student in the Neurosciences Program at the Stanford School of Medicine. "As you process the data, it can change."

Sacchet works in the lab of Stanford psychology Associate Professor Brian Knutson, who studies reward processing in a small area of the brain known as the nucleus accumbens. Precisely how that structure activates is at the heart of an ongoing debate about reward circuits – a subject that holds relevance for our understanding of everything from addiction to financial risk-taking.

Unfortunately, according to a paper from Knutson and Sacchet, hundreds of research papers on this circuit may be unintentionally biased. When the labs processed their fMRI findings, many used a one-size-fits-all strategy that skewed which regions of the brain appeared to be activating.

"I honestly think most people want good data," said Knutson. "I’m excited that we can make this kind of research more rigorous."

The paper appeared in the journal NeuroImage.

Too much smoothing

Functional magnetic resonance imaging measures changes in blood flow in the brain. It’s a powerful tool, but the signal fMRI actually detects – the result of the magnetic differences between oxygenated and deoxygenated blood – is noisy.

Researchers need to statistically process the data in order to make the resulting data interpretable. One of the most common approaches is known as “spatial smoothing,” which involves averaging the activity of each brain region with that of its neighbors.

But fMRI has only been in use since the mid-1990s. Many of the most common analyses in use today are holdovers from older, lower-resolution types of imaging and seem to have some undesired effects on the finer-grained signals fMRI can provide.

Knutson and Sacchet found that when researchers process fMRI data with a traditional “smoothing kernel” of 8mm, they end up averaging their images over too large an area. Activity in smaller brain structures can then be overlooked, or even shifted to areas that receive more blood flow and where the blood oxygenation level-dependent signal is stronger.

"It might seem strange that a systematic bias like that could bias the whole field," Knutson said. "But if half the people use 8mm and half use 4mm, you might end up with very different results, and it could add up."

Reward structure

These statistical pitfalls are particularly glaring when studying the small, structurally complex nucleus accumbens.

Findings from the Knutson Lab, which has been using the smaller, 4mm smoothing kernel for years, suggest that different parts of the nucleus accumbens have different functions. The forward portion seems to distinguish between positive or negative stimuli, reacting specifically to rewards. Meanwhile, the rear section responds more to the intensity of the motivation.

While some other labs have corroborated this finding, others only found activation in the rear half of the structure.

These contradictory findings now appear to have been skewed. Because the back of the nucleus accumbens is larger and surrounded by more blood-infused gray matter than the front, the smoothing step made it appear as if all the nucleus accumbens’ activity originated far to the rear.

A collaborator in Germany already has taken the paper’s advice, Sacchet said. “She had a colleague reanalyze her data and found the same thing we found.”

Knutson emphasized that the research paper doesn’t mean “the methods are bunk.” Simply improving the way scientists process signals can enhance their ability to locate specific brain functions.

"There may be a debate, but you can resolve that debate with data," he said.

How electrodes in the brain block obsessive behaviour

Deep brain stimulation helps some people with obsessive-compulsive disorder (OCD), but no one was quite sure why it is effective. A new study offers an explanation: the stimulation has surprisingly pervasive effects, fixing abnormal signalling between different parts of the brain.

A small number of people with difficult-to-treat OCD have had electrodes permanently implanted deep within their brain. Stimulating these electrodes reduces their symptoms.

To work out why stimulation has this effect, Damiaan Denys and Martijn Figee at the Academic Medical Center in Amsterdam, the Netherlands, and colleagues recorded neural activity in people with electrodes implanted into a part of the brain called the nucleus accumbens. This region is vital for conveying motivational and emotional information to the frontal cortex to guide decisions on what actions to take next. In some people with OCD, feedback loops between the two get jammed, leading them to do the same task repeatedly to reduce anxiety.

The researchers took fMRI scans as participants rested. In 13 people with OCD and implanted electrodes, there was continuous and excessive exchange of signals between the nucleus accumbens and the frontal cortex that was not seen in 11 control subjects. When the electrodes were activated, though, the neural activity of both brain regions in the people with OCD became virtually identical to that in the controls.

The researchers also used EEGs to monitor electrical activity in the brain as the 13 people with OCD viewed images linked with their obsessions, such as cleaning toilets. This time, the team observed excessive activity in the frontal cortex – and again, this activity disappeared when the electrodes were activated.

"The most striking thing is that stimulation doesn’t just affect the nucleus accumbens, but the whole network linked up with the cortex," says Figee.

The study suggests that the electrodes do more than normalise brain activity at the site where they are implanted, as had been assumed. Rather, they appear to repair entire brain circuits that had been faulty. “It resets and normalises these circuits,” says Figee.

Thomas Schlaepfer at the University of Bonn, Germany, points out that such work may allow researchers to use deep brain stimulation to learn about the causes of OCD as they treat it. “It will serve as a research platform informing us about the underlying neurobiology of such disorders,” he says.

(Image courtesy: Michael S. Okun)

Turning repulsive feelings into desires

Hunger, thirst, stress and drugs can create a change in the brain that transforms a repulsive feeling into a strong positive “wanting,” a new University of Michigan study indicates.

The research used salt appetite to show how powerful natural mechanisms of brain desires can instantly transform a cue that always predicted a repulsive Dead Sea Salt solution into an eagerly wanted beacon or motivational magnet.

Mike Robinson, a research fellow in the U-M Department of Psychology and the study’s lead author, said the findings help explain how related brain activations in people could cause them to avidly want something that has been always disliked.

This instant transformation of motivation, he said, lies in the ability of events to activate particular brain circuitry—a structure called the nucleus accumbens, which sits near the base of the front of the brain and is also activated by addictive drugs.

Cues for rewards often trigger intense motivation. The smell of food can make a person suddenly feel hungry when this wasn’t the case earlier. Drug cues may prompt relapse in addicts trying to quit. In some cases, desires may be triggered even for a relatively unpleasant event.

Researchers studied how rats responded to metal objects that represented either pleasant sugar or disgustingly intense Dead Sea saltiness. The rats quickly learned to jump on and nibble the sweetness cue, but turned away from and avoided the saltiness cue.

But one day the rats suddenly woke up in a new state of sodium appetite induced by drugs given the night before. On their first re-encounter with the saltiness cue in the new appetite state, their brain systems became activated and the rats instantly jumped on and nibbled the saltiness cue as though it were the sugar cue.

"The cue becomes avidly ‘wanted’ despite knowledge the salt always tasted disgusting," Robinson said.

The sudden brain changes help explain how an event, such as taking an addictive drug, could become “wanted” despite a person’s knowledge of the negative and unpleasant consequences of the drug.

"Our findings highlight what it means to say that drugs hijack our natural reward system," said Robinson, who authored the new study with Kent Berridge, James Olds Collegiate Professor of Psychology and Neuroscience.