Anxiety and dopamine

The Modulatory Role of Dopamine in Anxiety-like Behavior


. 2015 Sep;18(9):591-603.

Mohammad-Reza Zarrindast  1 , Fatemeh Khakpai  2



  • 1 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran, Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran, School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran, Institute for Cognitive Science Studies (ICSS), Tehran, [email protected].
  • 2 Institute for Cognitive Science Studies (ICSS), Tehran, Iran. [email protected].
  • PMID: 26317601


Mohammad-Reza Zarrindast et al. Arch Iran Med. 2015 Sep.

. 2015 Sep;18(9):591-603.


Mohammad-Reza Zarrindast  1 , Fatemeh Khakpai  2


  • 1 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran, Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran, School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran, Institute for Cognitive Science Studies (ICSS), Tehran, Iran. [email protected].
  • 2 Institute for Cognitive Science Studies (ICSS), Tehran, Iran. [email protected].
  • PMID: 26317601


Anxiety is an unpleasant physiological state in which an overreaction to a situation occurs. It has been suggested that different brain regions are involved in the modulation and expression of anxiety, including the amygdala, hippocampus, and frontal cortex. Dysfunction of neurotransmitters and their receptors can lead to many mood disorders like anxiety. There are evidences that dopamine plays an important role in anxiety modulation in different parts of the brain. Some evidence has shown that the mesolimbic, mesocortical and nigrostriatal dopaminergic system are involved in anxiety. Both dopamine D1 and D2 receptor mechanisms are important in mediating anxiety. The activity of dopaminergic system is modulated by several neurotransmitters, including glutamatergic neurons from the medial prefrontal cortex (mPFC), GABAergic fibers from the nucleus accumbens (NAc) as well as the ventral pallidum and cholinergic fibers from the pedunculopontine nucleus and the laterodorsal tegmental nucleus. Thus, changes in the glutamatergic, and GABAergic, as well as mediated transmission in the mesolimbic, mesocortical and nigrostriatal dopaminergic system may influence anxiety-like behavior.

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Dopamine primes the brain for enhanced vigilance | MIT News

Imagine a herd of deer grazing in the forest. Suddenly, a twig snaps nearby, and they look up from the grass. The thought of food is forgotten, and the animals are primed to respond to any threat that might appear.

MIT neuroscientists have now discovered a circuit that they believe controls the diversion of attention away from everyday pursuits, to focus on potential threats. They also found that dopamine is key to the process: It is released in the brain’s prefrontal cortex when danger is perceived, stimulating the prefrontal cortex to redirect its focus to a part of the brain that responds to threats.

“The prefrontal cortex has long been thought to be important for attention and higher cognitive functions — planning, prioritizing, decision-making. It’s as though dopamine is the signal that tells the router to switch over to sending information down the pathway for escape-related behavior,” says Kay Tye, an MIT associate professor of brain and cognitive sciences and a member of MIT’s Picower Institute for Learning and Memory.

When this circuit is off-balance, it could trigger anxious and paranoid behavior, possibly underlying some of the symptoms seen in schizophrenia, anxiety, and depression, Tye says.

Tye is the senior author of the study, which appears in the Nov. 7 issue of Nature. The lead authors are former graduate student Caitlin Vander Weele, postdoc Cody Siciliano, and research scientist Gillian Matthews.

Threat response

One major role of the prefrontal cortex, which is the seat of conscious thought and other complex cognitive behavior, is to route information to different parts of the brain.

In this study, Tye identified two populations of neurons in the prefrontal cortex, based on other brain regions that they communicate with. One set of neurons sends information to the nucleus accumbens, which is involved in motivation and reward, and the other group relays information to the periaqueductal gray (PAG), which is part of the brainstem. The PAG is involved in defensive behavior such as freezing or running.

When we perceive a potentially dangerous event, a brain region called the ventral tegmental area (VTA) sends dopamine to the prefrontal cortex, and Tye and her colleagues wanted determine how dopamine affects the two populations they had identified. To achieve that, they designed an experiment where rats were trained to recognize two visual cues, one associated with sugar water and one with a mild electrical shock. Then, they explored what happened when both cues were presented at the same time.

They found that if they stimulated dopamine release at the same time that the cues were given, the rats were much more likely to freeze (their normal response to the shock cue) than to head for the port where they would receive the sugar water. If they stimulated dopamine when just one of the cues was given, the rats’ behavior was not affected, suggesting that dopamine’s role is to enhance the escape response when the animals receive conflicting information.

“The reward-associated neurons drop their spiking by a substantial amount, making it harder for you to pay attention to a reward,” Tye says.

Further experiments suggested that dopamine acts by adjusting the signal-to-noise ratio in neurons of the prefrontal cortex. “Noise” is random firing of neurons, while the “signal” is the meaningful input coming in, such as sensory information. When neurons that connect to the PAG receive dopamine at the same time as a threatening stimulus, their signal goes up and the noise decreases. The researchers aren’t sure how this happens, but they suspect that dopamine may activate other neurons that help to amplify the signals already coming into the PAG-connected neurons, and suppress the activity of neurons that project to the nucleus accumbens.

Adapted for survival

This brain circuit could help give animals a better chance of surviving a threatening situation, Tye says. Any kind of danger sign, such as the snapping twig that startles a herd of deer, or a stranger roughly bumping into you on the sidewalk, can produce a surge of dopamine in the prefrontal cortex. This dopamine then promotes enhanced vigilance.

“You would be on the defensive,” Tye says. “There may be some times that you run when you don’t need to, but more often than not, it might make sense to turn your attention to a potential threat.”

Dysregulation of this dopamine-controlled switching may contribute to neuropsychiatric disorders such as schizophrenia, Tye says. Among other effects, too much dopamine could lead the brain to weigh negative inputs too highly. This could result in paranoia, often seen in schizophrenia patients, or anxiety.

Tye now hopes to determine more precisely how dopamine affects other neurotransmitters involved in the modulation of the signal-to-noise ratio. She also plans to further explore the role of this kind of modulation in anxiety and phobias.

The research was funded by the JPB Foundation, the Picower Institute Innovation Fund, the Picower Neurological Disorders Research Fund, the Junior Faculty Development Program, the Klingenstein Foundation, a NARSAD Young Investigator Award, the New York Stem Cell Foundation, the National Institutes of Health, the NIH Director’s New Innovator Award, and the NIH Pioneer Award.

Dopamine aversion | Science and life

Dopamine is needed not only for the feeling of pleasure, but also for the brain to be able to react to various troubles.

The neurotransmitter dopamine is commonly referred to when talking about feelings of pleasure and the reward (or reward) system. Any of our actions implies some kind of result, and we expect that this is the result that we will achieve - that is, we will receive a reward for our labors, even if the reward looks like just someone's "thank you". We feel the pleasure of the reward precisely because of the special neural circuits that use dopamine to transmit a signal between neurons. nine0003

Centers of the reward system (centers of pleasure and motivation) in the human brain. (Illustration by Fernando da Cunha / BSIP / Corbis)

Ventral tegmental area (VTA) and nucleus accumbens from the reinforcement system controlled by the prefrontal cortex. (Illustration by NIDA(NIH) /

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The dopamine response determines whether we continue to do what we were doing. If the reward exceeded expectations, the dopamine pleasure will be very large, if the reward met the expectations, then the dopamine pleasure will be less, but in general, we will still be motivated to act. If the reward did not live up to expectations, then dopamine chains will reduce activity, and motivation will disappear. Therefore, this system of nerve centers is called the reinforcement system - because positive experience from some of our actions is fixed in it. Manic addiction to something does not arise without her participation, and it is understandable why the reinforcement system is of great interest to physicians - many addictions, from food to drugs, develop because something went wrong in the pleasure centers. nine0003

At the same time, neuroscientists have long assumed that dopamine works not only in the neural circuits that serve the feeling of pleasure, but also in those that respond to irritating, unpleasant stimuli. However, most of the research is devoted to just "dopamine pleasure." The other side of dopamine is usually overlooked, because it requires experimenting with other neural circuits that lie apart from those that work with the feeling of pleasure. nine0003

To see "dopamine aversion," researchers at the University of California at Berkeley, along with colleagues from other research centers in the US, modified mouse dopamine neurons to fluoresce when they transmit nerve impulses; in turn, light signals from neurons were picked up by thin optical fibers injected directly into the brains of rodents. First of all, the authors of the work were interested in nerve cells that send signals to the nucleus accumbens, one of the main centers of the reinforcement system, which is often called simply the pleasure center. nine0003

An article in Neuron describes two neural pathways that ran from the ventral tegmental area (VTA) to the nucleus accumbens. The ventral tegmental region is located in the midbrain and also plays an important role in the reinforcement system; signals from the VTA diverge to a variety of brain centers. Some VTA neurons, whose processes go to the nucleus accumbens, fired in response to pleasurable stimuli. But other VTA neurons, which also went to the nucleus accumbens, were activated to unpleasant stimuli - for example, to a mild electric shock to the paws. In both cases, the neural circuits transmitted the signal with the help of dopamine. This signal came to different regions of the nucleus accumbens, which are located at a distance of only a few millimeters from each other. nine0003

It can be assumed that the signals of fear and disgust are needed by the reinforcement system in order to somehow evaluate the true benefit from the actions of the individual. After all, quite often for the sake of a reward you need to sacrifice something, and it would be good to understand whether the feeling of pleasure that results is really worth some sacrifices.

It can also be assumed that dangerous addictions develop precisely because the signals of aversion do not work correctly in the reinforcement system, and the person ceases to adequately assess his risk. Perhaps, by stimulating “dopamine aversion”, one can get rid of or at least mitigate a harmful addiction, but some medical prospects here will become clear only after additional studies on monkeys and humans. nine0003

By the way, dopamine is not the only neurotransmitter with such ambiguous behavior. It is known that the "love hormone" oxytocin, which is usually said to increase feelings of love and generally social attachment, can also stimulate feelings of anxiety and distrust towards an outsider. And the same can be said about serotonin, which is often called the “hormone of happiness” - some time ago we wrote that serotonin can cause depression if it affects certain neurons. nine0003

experts told about the benefits of hugs

The chance to hug anyone, even a stranger, is now given to every person around the world. All thanks to the International Hug Day, which is celebrated on January 21st. The correspondent of "MIR 24" learned from experts "" about the benefits of "hugs".

According to director of the Center for Multimodal Psychotherapy, dance movement therapist Maria Dolganova , in order to become happy, you need to hug at least ten times a day. According to neuropsychologists, people who are often hugged and touched a lot with love improve the ability of the brain to become aware of their body. Hugs and touches also increase levels of pleasure hormones in the blood: oxytocin, serotonin, and dopamine. nine0003

“As a rule, people who touch others easily are easier to establish emotional and close contact, easier to trust. Here, however, I would make a reservation: those who touch, being in good contact with their feelings and the other person, his reaction and the general context, ”says the expert.

According to Maria Dolganova, hugs relieve anxiety syndrome in children and adults, returning us to childhood, when we were small in the arms of our mother and felt safe. nine0003

“When we hug, excess tension leaves the body, the muscles relax. A calmer state of the body directly affects our emotions, the ability to express them openly. Remember the relaxed Spaniards or Italians! Hug with loved ones more often - according to science and following the principle of pleasure, there will be more joy from life! the expert concludes.

Psychologist, founder of the club “The way to yourself. Live consciously” Natalya Lukina also says that it is impossible to live life without embracing. nine0003

“Scientists have long studied and proven the positive effect of hugs on the human body and psyche (but only if they last more than 20 seconds). Huggers are less likely to get sick, do not overeat (since there is no desire to fill the void with food), age more slowly (they have lower stress levels and inflammatory processes in the body are not as aggressive), cheerful and joyful, but not in tension, have a good reaction and a sharp mind . However, you need to be careful. During hugs, oxytocin is actively produced, which strengthens the emotional attachment between partners. Therefore, you can not hug anyhow with anyone. However, if there is such an internal message, then it cannot be resisted, ”the expert says. nine0003

The complete absence of hugs can also lead to undesirable consequences, such as hallucinations.

“Every person has certain needs, including sensory ones, for example, to see or hear new information. The hormone dopamine is responsible for this, it makes us perceive. If a person is placed in a solitary cell, then after a while he begins to see and hear hallucinations: the brain itself initiates signals, without them it cannot. The same effect is now observed in sensory deprivation chambers, when a person is completely isolated from all sensory signals: visual, auditory, tactile,” says psychologist Alexander Shakhov.

According to the expert, people who have little contact with others have an increased level of anxiety and irritability. Other systems are also involved: there are difficulties in digestion, because cortisol (an alarm hormone) and adrenaline (a hormone to fight danger) primarily affect the gastrointestinal tract. Muscle spasms occur in certain muscle groups. A person feels anxiety and dissatisfaction, apathy, depression may occur. nine0003

“We often see that a person, getting into stressful situations or losing a loved one, instinctively reaches for hugs. We want to hug a person, cuddle up to him. Lonely people can hug a pillow or some object. Children, when afraid, begin to hug their toys. This is a need, and not just a form of social interaction,” continues Alexander Shakhov.

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