Therapeutic drugs that block dopamine receptors are most likely to reduce

SB 206553, a putative 5-HT2C inverse agonist, attenuates methamphetamine-seeking in rats

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Hormones and Neurotransmitters: The Differences and Curious Similarities

Quite curious indeed

Alpana and Murari ChaudhuriFollow Jun 26, 2018 · 3 min read A visualization of neurotransmitters. Source: Thermo Fisher Scientific.

Overview

Neurotransmitters and hormones are two different types of chemicals that carry signals from one part of the body to another. Both chemicals play an important part in the body’s physiology. They control a variety of physical and psychological functions, including our mood, our eating patterns, our ability to learn, and our sleep cycles.

The Differences

Hormones and neurotransmitters are different chemical messengers, the former produced by the endocrine glands and the latter by the nervous system.

Hormones are usually secreted from the endocrine system and released into the bloodstream, but they act on distant target cells. Some hormones, like melatonin and cortisol, are actually produced in the brain, released in the blood, and affect other parts of the body.

On the other hand, neurotransmitters are released from the presynaptic nerve terminal in the brain. They move across the synaptic cleft, a small space between two adjacent neurons, and move to the next neuron (known as a postsynaptic neuron). There they bind to specific receptors, causing changes in the electrical properties of target cells, which can cause various postsynaptic effects. Neurotransmitters work locally and their actions are very fast.

Both hormones and neurotransmitters influence our thoughts and motivations, as well as our ability to learn and concentrate. However, neurotransmitters’ actions are short-lived while hormones act for longer periods of time. Furthermore, neurotransmitters can affect both voluntary actions (eating, bathing, walking) and involuntary actions (breathing, blinking). Hormones in the endocrine system always work involuntarily.

Curious Similarities

Research in the last couple of years has demonstrated that some hormones, work like neurotransmitters independently of their classical hormone actions. The most well-studied hormones are progesterone and estrogen, which are known as steroid hormones.

Steroid hormones are typically synthesized in the endocrine gland and bind to a receptor that then binds to a specific DNA sequence, affecting gene transcription. This process is a lengthy one, which means that steroid hormones work for a prolonged period of time.

However, Progesterone and estrogen are also synthesized in the neuronal circuit, specifically in the presynaptic terminal. They then bind to the membrane and intracellular receptors followed by neurotransmitter-like action, which is very fast and short-lived. These neurotransmitters-like steroids have multiple receptors. The steroid-receptor specific functions are not yet clearly understood.

Some well-studied neuroreceptors, like dopamine and serotonin are known to possess hormonal functions. Dopamine is a neurohormone released from the hypothalamus; its main function is to block the release of prolactin, another hormone, from the pituitary gland. As a neurotransmitter released from the central nervous system, it also has many functions including roles in cognition and motor activity.

Adrenaline and noradrenaline are two molecules that differ by one carbon atom. Adrenaline, which is produced by the adrenal gland, acts as a hormone. On the other hand, noradrenaline acts as a neurotransmitter in the central nervous system.

This is just a piece of a growing body of research suggesting that many hormones work as neurotransmitters and vice-versa. The next area of research here is to determine the receptor-specificity of these molecules to understand how their function may change depending on the receptor and mode of binding.

Further Reading

S.F. Owen, et al. (2013). Nature, 500, 458–462.

B.J. Martin, et al. (2015). Nature, 520, 499–504.

Lauren M. Rudolph, et al. (2016). The J. of Neuroscience, 36, 11449–11458.

Balthazart, J. & Ball, G.F. (2006). Trends Neurosci., 29, 241–249.

Dopamine

loveExamining the roles of various hormones as a person experiences love.© American Chemical Society (A Britannica Publishing Partner)See all videos for this article

Dopamine, also called hydroxytyramine, a nitrogen-containing organic compound formed as an intermediate compound from dihydroxyphenylalanine (dopa) during the metabolism of the amino acid tyrosine. It is the precursor of the hormones epinephrine and norepinephrine. Dopamine also functions as a neurotransmitter—primarily by inhibiting the transmission of nerve impulses—in the substantia nigra, basal ganglia, and corpus striatum of the brain.

Read More on This Topic nervous system: Dopamine Dopamine is a precursor of norepinephrine that acts as a neurotransmitter at certain synapses of the brain. Disorders at…

A deficiency of dopamine associated with cellular death in the substantia nigra results in Parkinson disease. Dopamine-receptor agonists, which bind to dopamine receptors on dopamine-producing neurons in the neurotransmitter’s absence, can increase dopaminergic activity in the brain, helping to lessen Parkinson symptoms.

Abnormalities in dopamine transmission, including hyperactive dopamine transmission in certain parts of the brain, have been linked to psychotic syndromes such as schizophrenia. Dopaminergic structures within the brain, such as the striatum and nucleus accumbens, have also been implicated in reward-related behaviour.

What Is Dopamine?

Some street drugs can mimic the effects of dopamine, an important neurotransmitter.

Dopamine helps communicate messages across different parts of the brain, and between the brain and the rest of the body. iStock

Dopamine is a neurotransmitter that helps send signals in the brain. (1)

Neurotransmitters are chemicals made by nerve cells called neurons. They’re used to communicate messages across different parts of the brain and between the brain and the rest of the body.

Dopamine is involved mainly in controlling movement. An insufficient production of dopamine in part of the brain can lead to Parkinson’s disease. Parkinson’s diseases is a noncurable nervous system disorder that affects movement. It may cause stiffness, tremors, shaking, and other symptoms. (1)

How Dopamine Works Inside the Brain’s Reward System

Dopamine plays a role in the brain’s reward system, helping to reinforce certain behaviors that result in reward. A surge of dopamine, for instance, is what prompts a laboratory rat to repeatedly press a lever to get a pellet of food, or a human to take a second slice of pizza. (2)

Recently, scientists have shown that dopamine can help with unlearning fearful associations. In a study published in June 2018 in the journal Nature Communications, researchers uncovered the role of dopamine in lessening fearful reactions over time, an important component of therapy for people with anxiety disorders, such as phobias or post-traumatic stress disorder (PTSD). (3)

More on the Brain and Dopamine

Dopamine also helps to aid the flow of information to the brain regions responsible for thought and emotion. According to the National Institute of Mental Health, too little dopamine — or problems in the way the brain uses dopamine — may play a role in disorders such as schizophrenia or attention deficit hyperactivity disorder (ADHD). (1)

Dopamine and the Body’s Stress Response

In other parts of the body, dopamine acts as type of hormone called a catecholamine. Catecholamines are made in the adrenal glands — small hormone production factories that sit on top of the kidneys. (4)

There are three main catecholamines:

  • Dopamine
  • Epinephrine (adrenaline)
  • Norepinephrine

These hormones get released into the bloodstream when the body is physically or mentally stressed. They cause biochemical changes that activate the so-called fight-or-flight response. That’s the body’s natural reaction to a real or perceived stress. (4)

Dopamine has many functions outside the brain. It acts as a vasodilator, helping to widen blood vessels. It helps to increase urine output in the kidneys, and in the pancreas it reduces the production of insulin, a hormone involved in blood sugar regulation. (5)

Dopamine and Digestion

Dopamine also plays a role in the digestive system, helping to make sure the contents of the gastrointestinal tract don’t pass through too quickly. In the immune system, dopamine dampens inflammation, normally helping to prevent the sort of runaway immune response seen in autoimmune diseases. (5)

What Are Dopamine Receptors?

Dopamine receptors are proteins found in the brain and nerves throughout the body. If neurotransmitters are the nerve cells’ chemical messengers, then receptors are the nerve cells’ chemical receivers. (6)

As a dopamine signal approaches a nearby neuron, it attaches to that neuron’s receptor. The receptor and neurotransmitter work like a lock and key. The dopamine attaches to the dopamine receptor, delivering its chemical message by causing changes in the receiving nerve cell.

Why Dopamine Receptors Are Key for Neurological and Physical Functions

Dopamine receptors play an important role in many neurological processes, including movement coordination and fine motor control, pleasure, cognition, memory, and learning.

Abnormally functioning dopamine receptors may play a role in several neurological and psychiatric illnesses. Therefore, dopamine receptors are a natural target for many drug therapies.

Some street drugs, including heroin, cocaine, and methamphetamine, also act on dopamine receptors in the brain. They can cause nerve cells to release too much dopamine or prevent the nervous system from recycling dopamine once it’s done its job, highjacking the brain’s reward system. (7)

Euphoric Effects, Pleasure, and Dopamine

Dopamine creates feelings of pleasure. Certain drugs, such as cocaine, can cause large amounts of dopamine to flood the system, producing euphoric effects or a “high” that leave the user wanting more. (7)

As these drugs are abused over time, dopamine’s pleasurable effects on the brain lessen.

To regain these pleasurable effects, a user must increase the amount of drug taken. This phenomenon is called “tolerance.”

Dopamine Drugs

There are a few classes of medication that work on the dopamine pathways of the brain to treat disease. They include:

Levodopa (L-dopa) Levodopa is a drug used to treat Parkinson’s disease. Symptoms of Parkinson’s disease start to show up when dopamine-producing cells in the brain die. Levodopa, a precursor chemical to dopamine, helps to boost dopamine levels in the brain. Once levodopa reaches the brain, it transforms into dopamine. (8)

Dopamine Agonists Dopamine agonists are a class of drugs that bind to and activate dopamine receptors in the brain. They mimic the action of naturally-occurring dopamine in the brain, causing the neurons to react as they would to dopamine. (9)

Dopamine agonists trick the brain into thinking it’s getting the dopamine it needs.

Dopamine agonists are used to treat low dopamine conditions, including Parkinson’s disease and restless legs syndrome (RLS). RLS is a sleep disorder that causes an unpleasant tingling or twitching sensation in the legs when lying or sitting down, mostly at night, resulting in an irresistible urge to move them, and in insomnia. Like Parkinson’s disease, it too seems to be caused by a dopamine shortage in the brain. (10)

Dopamine agonists also are sometimes used to treat depression and fibromyalgia.

Common dopamine agonist drugs include: (9)

  • Mirapex (ramipexole)
  • Neupro (rotigotine)
  • Requip (ropinirole)

Serious side effects associated with dopamine agonists include low blood pressure, dizziness when standing up, hallucinations, and impulse control disorders, such as pathological gambling, compulsive eating, and hypersexuality.

Dopamine Antagonists Dopamine antagonists are a class of drugs that bind to and block dopamine receptors. Dopamine antagonists turn down dopamine activity, which may be useful for the treatment of psychiatric conditions such as schizophrenia and bipolar disorder, which have been associated with an overactive dopamine system.

Many antipsychotic drugs are dopamine antagonists, working to block dopamine receptors in the brain.

Dopamine antagonists that act on dopamine receptors in the gastrointestinal tract may be used to treat nausea, or as anti-emetics to stop vomiting.

Dopamine antagonist drugs include:

  • Thorazine or Largactil (chlorpromazine)
  • Reglan (metoclopramide)
  • Phenergan (promethazine)
  • Invenga (paliperidone)
  • Risperdal (risperidone)
  • Seroquel (quetiapine)
  • Clozaril (clozepine)

Dopamine Supplements and Supplementation

Dopamine is found in many types of food, but dopamine itself can’t cross into the brain from the bloodstream, so eating foods that contain dopamine won’t raise dopamine levels in the brain. But dopamine’s precursor molecule, tyrosine, can cross the blood-brain barrier, according to a review published in November 2015 in the Journal of Psychiatric Research. (11)

Tyrosine is an amino acid found naturally in protein-rich foods, such as cheese, nuts, and meat. (12) Under certain circumstances, tyrosine supplements can help boost dopamine levels in the brain, leading some to believe that tyrosine supplementation could help with neurological and mental health conditions involving low dopamine. In fact, the Parkinson’s disease drug Levodopa was originally synthesized from one form of tyrosine.

But scientific studies have failed to show that this is the case. Tyrosine supplements don’t appear to have much — if any — effect on physiology, thought, or behavior. (11)

News & Research

Among the brain’s many chemical messengers, few stand out as much as the neurotransmitter dopamine. Linked to love, pleasure, motivation and more, dopamine signaling plays a central role in the brain’s reward system. It is also critical for processes such as motor control, learning and memory.

Malfunctioning dopamine neurons have been implicated in numerous disorders, including Parkinson’s, schizophrenia and addiction. Because of its importance in the brain, researchers have studied the neurotransmitter for decades, making great progress in understanding its activity and when it goes awry.

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Less is known, however, about the mechanisms that healthy dopamine cells use to release the neurotransmitter, a gap that has limited scientists’ ability to develop treatments for a range of dopamine-related conditions.

Now, researchers from Harvard Medical School have for the first time identified the molecular machinery responsible for the secretion of dopamine in the brain.

Their work, published online in Cell on Feb. 1, identifies specialized sites in dopamine-producing neurons that release dopamine in a fast, spatially precise manner—a finding that runs counter to current models of how the neurotransmitter transmits signals in the brain.

“The dopamine system plays an essential role in many diseases, but fewer studies have asked the fundamental question of how healthy dopamine neurons release the neurotransmitter,” said senior study author Pascal Kaeser, assistant professor of neurobiology at HMS.

“If your car breaks down and you want it fixed, you want your mechanic to know how a car works,” he added. “Similarly, a better understanding of dopamine in the laboratory could have a tremendous impact on the ability to treat disorders in which dopamine signaling goes awry in the long term.”

Dopamine research has largely centered on its dysfunction and on the protein receptors that neurons use to receive dopamine, said Kaeser. Despite the neurotransmitter’s importance, studies on how it is released in the brain under normal circumstances have been limited, he added.

Promiscuous No More

To identify the molecular machinery responsible for dopamine secretion, Kaeser and his colleagues focused on dopamine-producing neurons in the midbrain, which are involved in the neural circuitry underlying movement and reward seeking.

They first searched for active zones—specialized neurotransmitter release sites located at synapses, the junctions that connect one neuron to the another. Using super-resolution microscopy to image sections of the brain into which dopamine neurons project, the team found that dopamine neurons contained proteins that mark the presence of active zones.

These zones indicate that a neuron may engage in fast synaptic transmission, in which a neurotransmitter signal is precisely transferred from one neuron to another within milliseconds.

This was the first evidence of fast active zones in dopamine neurons, which were previously thought to engage in only so-called volume transmission—a process in which the neurotransmitter signals slowly and nonspecifically across relatively large areas of the brain.

Active zones were found at lower densities in dopamine neurons than in other neurons, and additional experiments revealed in detail how the neurotransmitter is rapidly secreted and reabsorbed at these sites.

“I think that our findings will change how we think about dopamine,” Kaeser said. “Our data suggest that dopamine is released in very specific locations, with incredible spatial precision and speed, whereas before it was thought that dopamine was slowly and promiscuously secreted.”

In another set of experiments, the researchers used genetic tools to delete several active zone proteins. Deleting one specific protein, RIM, was sufficient to almost entirely abolish dopamine secretion in mice. RIM has been implicated in a range of diseases including neuropsychiatric and developmental disorders.

Deleting another active zone protein, however, had little or no effect on dopamine release, suggesting that dopamine secretion relies on unique specialized machinery, the authors said.

“Our study indicates that dopamine signaling is much more organized than previously thought,” said study first author Changliang Liu, an Alice and Joseph Brooks Postdoctoral Fellow and a Gordon Fellow in the Kaeser lab.

“We showed that active zones and RIM, which is associated with diseases such as schizophrenia and autism spectrum disorders in human genetic studies, are key for dopamine signaling,” Liu said. “These newly identified mechanisms may be related to these disorders and may lead to new therapeutic strategies in the future.”

The team is now working to investigate these active zones in greater detail to build a deeper understanding of their role in dopamine signaling and how to manipulate them.

“We are deeply invested in learning the entire dopamine signaling machine. Right now, most treatments supply the brain with dopamine in excess, which comes with many side effects because it activates processes that shouldn’t be active,” Kaeser said.

“Our long-term hope is to identify proteins that only mediate dopamine secretion,” he said. “One can imagine that by manipulating the release of dopamine, we may be better able to reconstruct normal signaling in the brain.”

Additional authors on the study include Lauren Kershberg, Jiexin Wang and Shirin Schneeberger of the Department of Neurobiology at Harvard Medical School.

This study was supported by the National Institutes of Health (R01NS083898, R01NS103484), the Harvard Brain Initiative, the Goldenson Foundation, the Lefler Foundation and the Gordon Center for the Cure and Treatment of Paralysis.

What Is Dopamine And How Does It Affect The Brain And The Body?

By Jon Jaehnig

Updated November 20, 2019

Reviewer Jeffrey Craven , MA, LMHC, LPCC, LLC

If you’ve ever taken a psychology course, you’ve probably heard the word “dopamine.” It’s one of the most well-known of the body’s many neurotransmitters, with over 110,000 research papers to its name. But though many of us have heard of dopamine, few of us understand it. So, what exactly is dopamine and how does it affect the brain and the body? Let’s take a closer look.

Confused About How Dopamine Affects Your Brain? Ask A Psychologist. Chat With A Board-Certified Psychologist Online Today.

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What Is Dopamine?

Dopamine is a neurotransmitter-a chemical messenger that sends information in between neurons. Neurons are the basic units of our nervous system, which includes the brain, spinal cord, nerves, and sense organs (like ears and eyes). It is most commonly associated with the brain’s pleasure and reward system. It also plays a role in controlling movement.

Dopamine can be found in two different areas of the brain. The first is the substantia nigra, which plays a role in both rewards and movement. The dopamine in the substantia nigra consists of the cells that die when someone has Parkinson’s disease, which causes the tremors and other mobility difficulties that are characteristics of the condition.

Most of the dopamine in your body is produced in the ventral tegmental area (VTA) of the brain, which is the main player in the brain’s pleasure and reward signaling. Dopamine is created in the VTA and then released into other areas of the brain when someone does something that warrants a reward or pleasure response, or even when a person just anticipates a reward. Though most people associate a reward in the brain with behaviors like drug use or sex, dopamine also responds to behaviors that we need to survive, like eating or drinking water.

Humans need to experience some sort of a reward response through dopamine for these necessary behaviors in order to motivate us to keep doing them. Releasing dopamine, causing us to feel pleasure, is our body’s mechanism to ensure we continue the necessary activities for good health.

Dopamine vs. Serotonin

Dopamine is often grouped with another neurotransmitter called serotonin. While the two neurotransmitters do have some similarities in that they are both chemical messengers for the brain, and both have positive associations in regards to mood, their core functions are quite different. Dopamine brings about positive feelings based on a certain action. Serotonin, on the other hand, functions more as a mood stabilizer. However, a deficiency in either serotonin or dopamine can negatively affect overall mood and happiness.

What Does Dopamine Do?

Dopamine’s two primary functions are motivation and movement. However, dopamine also plays a role in other cognitive functions such as memory and focus.

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Dopamine and Movement

As previously mentioned, dopamine produced in the substantia nigra (part of the basal ganglia region of the brain) helps control movement. The basal ganglia control many aspects of bodily movement and rely on the secretion of dopamine from dopamine-containing neurons to function properly. Thus, dopamine is necessary for the controlled movement to occur in its normal fashion.

However, sometimes this facilitation is disrupted, and not enough dopamine reaches the substantia nigra and basal ganglia. When this happens, movement and control of movement and motor functions are greatly reduced. One of the main symptoms of Parkinson’s disease is delayed or uncontrollable movements, which researchers have found is caused by a lack of dopamine in the substantia nigra.

Conversely, sometimes the basal ganglia are overloaded with dopamine. While a lack of dopamine restricts movement, too much dopamine can cause the body to make too many movements. These uncontrolled, unnecessary movements are a common characteristic of Tourette’s syndrome.

Dopamine, Pleasure, and Rewards

Dopamine is the primary neurotransmitter involved in the brain’s rewards system and feelings of pleasure. When someone engages in behavior the brain perceives as pleasurable, such as eating, dopamine is released, and the behavior is signaled as one that merits a reward. This motivates the person to perform the behavior again in the future. Another common dopamine trigger is sex. Sexual intercourse sparks the release of dopamine, along with hormone and neurotransmitter oxytocin. These two things are what cause the euphoric feelings around sex and contribute to the human desire to engage in sexual intercourse.

Confused About How Dopamine Affects Your Brain? Ask A Psychologist. Chat With A Board-Certified Psychologist Online Today.

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While the reward system is designed to motivate us to carry out behaviors that benefit our health, it can also motivate certain harmful behaviors when dopamine is artificially stimulated. One example of this is cocaine. This drug blocks the reuptake of dopamine, meaning that the brain’s synapses are flooded with an unusually high amount of the neurotransmitter. This excess of dopamine leads to the euphoric feeling one may experience after using the drug. But it also interferes with the brain’s natural dopamine system and can disrupt its normal cycles.

Despite feeling unusually euphoric immediately after using cocaine, in the long run, it causes someone to feel worse because the dopamine system does not function as it should. The brain responds to the extremely high levels of dopamine released due to drugs by naturally producing less dopamine on its own.

Dopamine and Addiction

The rush of dopamine experienced when using cocaine and other drugs also contributes to drug addiction. Because the brain experiences extremely high amounts of dopamine when someone uses drugs, usage of the drug becomes associated with rewards and pleasure. This means the person will be motivated to repeat the behavior to experience the same reward. Unfortunately, this can rope someone into the cycle of addiction.

Not only does someone become addicted, but they also will want to use higher amounts of the drug. The brain builds a tolerance to the drug and produces less dopamine when the person uses it, so they will have to use more and more of the drug to feel the same rush of dopamine as they did upon initial usage. Keep in mind that drugs can cause a release of two to ten times more dopamine than natural triggers like eating or sex.

The dopamine cycle is just one of the reasons why breaking an addiction is so incredibly challenging. Most people cannot overcome addiction on their own. A therapist or counselor can be a great person to have as part of your support system if you are struggling with addiction.

Dopamine and Memory

One of the lesser-known dopamine functions is its role in memory. Though dopamine is not produced in the prefrontal cortex area of the brain, dopamine secretions in that area help facilitate memory processing. This is a highly delicate function of dopamine, so even the slightest variation in the number of dopamine secretions in the area can severely impact one’s memory.

Dopamine can also explain why we best remember things that interest us. When something is interesting to us or excites us, we get a spike of dopamine because the experience of learning about that thing is pleasurable. The dopamine secretes in the prefrontal cortex, so our memory is activated, and we are more likely to remember whatever we’re learning about. When we find the subject boring, we do not have the same dopamine spike, so there is less dopamine in the prefrontal cortex, and thus it is harder for us to remember what we learned.

Teachers can greatly benefit from this information. Teaching in a way that stimulates students and invokes the brain’s reward center, by having students participate in an activity or another engaging teaching method, can help students better remember the information.

Dopamine and Focus

Another dopamine function that teachers may want to be aware of is its role in focus and attention. Dopamine responds to the optic nerves (those used for vision) to help someone focus their attention on a specific activity. When visually focusing on something, dopamine can help us keep things in our short-term memory. It is thought that low levels of dopamine in the prefrontal cortex may contribute to attention deficit disorder.

Source: pexels.com

Dopamine and Happiness

As previously mentioned, dopamine is sometimes confused with another neurotransmitter, serotonin. Unlike serotonin, dopamine does not directly help control mood. However, it can still influence moods and emotions. Because it can bring about feelings of pleasure, dopamine is associated with feeling satisfied with a certain event or one’s life in general, which certainly can influence happiness.

Some research also suggests that dopamine may play a role in depression. Whatever the cause of depression may be, therapy or counseling is a great tool for many people to manage their condition.

Dopamine and Sleep

Dopamine helps us feel more awake, and the body naturally produces more of it during daytime hours when we are more stimulated. As night falls, dopamine levels fall as well, helping us feel tired and ready for bed. People with low dopamine or with conditions such as Parkinson’s, which is associated with low dopamine levels, may feel chronic tiredness during all hours of the day.

How BetterHelp Can Support You

If you’ve been suffering from depression due to a dopamine production issue-or for any other reason, it may be time to get professional help.

BetterHelp’s licensed professionals provide discreet and anonymous online counseling. BetterHelp has your back, no matter how severe you feel your depression may be. Avoid all the stress of traveling to meet a therapist in person and talk with a counselor today. Read below for some reviews of BetterHelp counselors.

Counselor Reviews

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Conclusion

Dopamine is an extraordinary part of our brain and body that helps us feel happiness, among other emotions. If you believe you may have a dopamine issue, there are tools available for you to move forward to a healthier and happier life. Take the first step.

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