Understanding Dopamine: From Reward Pathways to Neurological Disorders

Dopamine is a monoamine neurotransmitter, a chemical messenger functioning like a reward center in the brain responsible for motivation and elevation of mood. Dopamine is released when one engages in pleasurable activities like baking cookies, social interactions, sex, or even binge- watching your favorite shows. Runner’s high is depicted by dopamine release related to boost in mood and a sense of achievement.

Moreover, high-risk activities like gambling or ingesting substances like caffeine, nicotine or alcohol have characteristic features similar to euphoria which is explained by the dopamine release. Dopamine imitates the function of a peripheral hormone. It is an endogenous catecholamine derived from the amino acid tyrosine and is produced by adrenal gland influencing many physiological responses like heart rate and blood pressure.

Kidneys, pancreas, lungs and numerous blood vessels outside central nervous system (CNS) have dopamine receptors. Renal dopamine is crucial for regulation of electrolytes particularly sodium. Dysfunctions in dopamine pathways or abnormal renal dopamine production may endorse hypertension in humans and even animals.

Role of Dopamine as a Neurotransmitter:

• Motivation and reward
• Mood elevation and satisfaction
• Cognition: memory and learning
• Sleep regulation and arousal
• Attention and concentration
• Movement
• Stress response
• Pain processing

Role of Dopamine as a Hormone:

• Vasoconstrictor and vasodilator
• Increases Sodium removal from the body
• Reduces insulin production in Pancreas
• Reduces gastrointestinal (GI) movement and protects GI lining
• Reduces the efficacy of the immune system (circulation and activity of lymphocytes – white blood cells)

Thus, regulation of dopamine is essential in order to perform the aforementioned functions. Imbalance of the same or any dysfunction in its pathway leads to neurological or psychological disorders like Parkinson’s disease, depression, addiction, schizophrenia, ADHD (attention-deficit hyperactivity disorder), obesity.

Parkinson’s disease and Dopamine:

Parkinson’s disease is a neurodegenerative disorder of the (CNS) central nervous system. It is associated with deficiency of dopamine due to nerve cell damage in substantia nigra which controls movement. It is marked by problems with balance, slow movement (bradykinesia), tremors, and muscle stiffness (rigidity).

According to National Institute of Neurological Disorders and Stroke, people affected with Parkinson’s disease lose 60-80% of the dopamine-producing cells in the substantia nigra. Dopamine is a neurotransmitter which transmits impulses between substantia nigra and corpus striatum which constitutes basal ganglia, responsible for balance and movement. Moreover, reduced dopamine levels cause drowsiness in patients with Parkinson’s disease. L-dopa or Levodopa or Carbidopa drug boosts the production of dopamine and the person affected with Parkinson’s disease shows improved symptoms.

Schizophrenia and Dopamine:

Abnormalities of the inhibitory neurotransmitter dopamine might endorse schizophrenic symptoms of hallucinations and delusions. It is characterized by high levels of dopamine receptors in the pre-frontal cortex and mesolimbic areas of the brain. Moreover, antipsychotic drugs which have agonist properties increase the dopamine levels in the pre-frontal cortex along with the stress levels. Although, dopamine along with serotonin pathways contribute to the Parkinson’s disease. Neurotensin is an endogenous peptide which is similar to dopamine anatomically and functionally. Abnormalities in the same might lay the foundation for schizophrenia (Kinkead, 2006).

Substance-use disorders and dopamine:

Substance-use disorders are divided into six categories – depressants, stimulants, opioids, hallucinogens, other drugs and gambling disorder. Continuous use of the above drugs creates dependence for the same where the body craves for the drugs. The neurobiological cause behind this mechanism consists of the meso-cortico-limbic-dopamine pathway, where ventral tegmentum serves as the pleasure center in the limbic system which is responsible for emotions, memory and gratification of needs.

Whenever a substance is ingested this pathway is activated and becomes reinforced if taken for a prolonged period of time. Thus, the tolerance increases as the reward center is overstimulated over repeated exposure to recreational drugs. The stimulation caused by these drugs builds up an individual’s tolerance which indicates that the previously administered amounts of drugs no longer produces the same effect, causing the body to desire for increased amounts.

Either the brain attempts to decrease the production of dopamine or reduces the dopamine receptors, thus craving for increased amounts of drugs is observed post intake of a drug for an extended period of time. Moreover, stimulants like cocaine prevents the reuptake mechanism of dopamine, further leading to increase in dopamine production leading to euphoric state. Increased levels of dopamine cause alertness when recreational drugs like cocaine and amphetamines are administered.

ADHD and dopamine:

Attention-deficit hyperactivity disorder is a neurodevelopmental disorder marked by hyperactivity, impulsivity and inattention. Dopamine abnormalities might be associated with the pathology of ADHD. Amphitamines are used for the treatment of this disorder despite its stimulating properties. Furthermore, stimulants like amphitamines are exemplified to increase the accessibility of dopamine in the brain.

Depression and Dopamine:

Major depressive disorder (MDD) is characterized by low pervasive mood with a loss of interest in daily activities (anhedonia). It is 8-12% prevalent across the globe. Anhedonia is majorly considered to be closely linked to the abnormalities in the dopamine system (Markou, 2012) which regulates reward anticipation, disruption in motivation and decision-making process. Studies have shown that amphitamines (stimulants) if administered to MDD patients would result in a pattern of euphoria (Tremblay et al., 2002).

Eating disorders and Dopamine:

From an evolutionary perspective, pleasure was linked to eating as a survival strategy. When food was scarce, the brain incentivized humans to go to great lengths to secure enough nourishment. Highly palatable foods, like those rich in sugar, salt, and fat, can trigger a significant dopamine release. This surge in dopamine not only elevates mood while eating but also intensifies cravings for these foods. This mechanism parallels the way drug addiction works, activating similar brain regions in response to these substances.

The smell of the cookies often increases our motivation to eat them causing a dopamine rush. For an individual with binge-eating disorder or during the binging episodes of an individual with bulimia nervosa this response is even stronger and thus gets reinforced after each episode. The early release of dopamine might also account for the loss of control over eating habits even when the affected individuals with binge-eating disorder or bulimia nervosa are not hungry.

Obesity and Dopamine:

Dopamine receptor availability was diminished in obese individuals in relation to their BMI. Given dopamine’s role in regulating motivation and reward pathways, a deficiency in dopamine among obese individuals may contribute to compulsive eating as a way to offset the decreased activation of these circuits. Strategies aimed at enhancing dopamine function may offer potential benefits in obesity treatment (Wang et al., 2001).

Bipolar Disorder and Dopamine:

Bipolar disorder is a significant mental health condition characterized by frequent or alternate episodes of mania or depression. Hyperdopaminergia (high levels of dopamine) drives the onset of manic symptoms including high energy levels, then hypodopaminergia (low levels of dopamine) could be linked to the depressive phase of the disorder manifested as a low pervasive mood. The inter-episode mood instability is accounted by dopamine imbalances which further defines the opposing affective poles of the disorder. Antipsychotic drugs like risperidone or olanzapine are dopamine antagonists used for treatment of the same.

Dopamine Agonists:

These substances replicate the effects of dopamine by binding to its receptors, causing nerve cells to behave in the same way they would with natural dopamine. It’s used in the treatment of Parkinson’s disease, ADHD (attention-deficit hyperactivity disorder) and clinical depression – ailments associated with low dopamine levels where dopamine agonists increase the levels of the same.

Dopamine Antagonists:

Dopamine antagonists are medications that attach to and obstruct dopamine receptors on nerve cells in the brain. This blockage stops dopamine from reaching the subsequent nerve cell. Many antipsychotic drugs categorized as dopamine antagonists are used in the treatment of schizophrenia and bipolar disorder, which reduces the activity of dopamine since the mentioned disorders are associated with high levels of the same.

Dopamine Reuptake Inhibitors:

Dopamine reuptake inhibitors are medications that block the re-entry and reabsorption of dopamine by the presynaptic neuron that released it. This results in a higher concentration of dopamine available to other neurons in the brain. It’s used in the treatment of depression, substance-use disorders (cocaine, nicotine) and obesity (binge-eating and overeating).

Symptoms of high dopamine:

• Euphoria – state of extreme happiness
• Intensifies sex drive
• Aggressive – poor impulse control
• Elevated energy levels
• Problematic sleep cycle

Symptoms of low dopamine:

• Anhedonia – displays low interest in activities of daily living
• Difficulty concentrating – inattention
• Reduced energy levels
• Minimal to low sex drive
• Trouble sleeping
• Pervasive low mood – sadness/unhappy
• Lacking motivation
• Memory loss

Serotonin and dopamine:

Serotonin and dopamine are neurotransmitters which are essential for metabolism and sleep-wake cycles. They boost positive mood and emotions, although dopamine is associated with reward and motivation whereas serotonin is related to happiness and mood. Imbalance in any of their pathways may lead to detrimental effects on digestion and sleep.

• In cases of clinical depression, dysfunction in dopamine systems might be manifested as low motivation, anhedonia (reduced interest in activities of daily living) and feeling helpless. Although abnormalities in serotonin pathways may not be the direct cause of depression, research indicates that SSRIs (selective serotonin reuptake inhibitors) improve symptoms in 40-60% of individuals over a 6 to 8-week period, primarily by enhancing positive emotional processing.

• Both dopamine and serotonin are involved in digestion, though serotonin plays a larger role by aiding in peristaltic movement along the gut. Meanwhile, dopamine primarily supports the release of insulin from the pancreas.

• The pineal gland regulates the sleep-wake cycle by assessing the varying range of light stimulus. These signals are transmitted via neurotransmitters such as serotonin and dopamine, leading to the production of melatonin. Dopamine in the pineal gland offsets the effects of norepinephrine, a chemical messenger that is involved in the production of melatonin. When dopamine is active, melatonin production decreases, leading to heightened alertness. Whereas, serotonin aids in the suppression of rapid eye movement (REM) sleep. Additionally, research studies have found that elevating serotonin levels through SSRIs reduces REM sleep. In the brain’s dorsal raphe nucleus, increased serotonin levels lead to wakefulness. Although, it serves as a predecessor to melatonin, the primary hormone regulating sleep. Thus, the body depends on serotonin from the pineal gland to produce melatonin inducing sleep.

• Impulsive aggression is a behavioral comorbidity of depression and substance-use disorders marked by difficulty controlling negative emotions and urges to cause harm to oneself or others. Studies suggest that diminished serotonergic activity in brain regions involved in emotion regulation, like the prefrontal cortex and anterior cingulate cortex, may significantly contribute to a predisposition for impulsive aggression. Additionally, serotonergic dysfunction can result in heightened dopaminergic system activity, further intensifying impulsive and aggressive behaviors.

A diet that includes ingredients high in tyrosine and magnesium aid in elevating dopamine levels. Tyrosine, a nonessential amino acid, is produced in the body from another amino acid called phenylalanine, which is crucial for dopamine synthesis. Consuming the following foods can help naturally boost dopamine levels:

• Legumes
• Soy products
• Dairy products
• Nuts and seeds
• Fish – salmon and tuna
• Whole grains – oats and quinoa
• Poultry items – chicken and turkey
• Fruits and green-leafy vegetables – tomatoes, bananas, avocados, oranges and peas

Supplements:

• Tyrosine
• Omega-3 essential fatty acids
• Magnesium
• Vitamin D, B5 and B6
• L-theanine
• Psychobiotics
• Velvet bean

Dopamine detox:

Dopamine detox is an approach of cognitive behavioral therapy (CBT) developed by Cameron Sepah to treat individuals affected with impulsivity and addiction. This technique incorporates resilience where an individual learns to control their impulses and indulges in response prevention which used to result in immediate satisfaction.

The myth about dopamine detox is excluding all pleasurable activities from an individual’s life, curbing their reward and motivation. Instead, dopamine detox results in the prevention of problematic activities which results in immediate gratification of needs and leads to pleasure and is detrimental to one’s life. Such activities include:

• Pleasure eating or emotional eating
• Gaming disorder or internet addiction
• Pornography or masturbation
• Risky activities and thrilling experiences
• Consuming recreational drugs
• Gambling disorder
• Impulsive purchasing

The objective is to reset your brain’s reward system, prevention of sensitivity towards the rewards and gratification, and develop greater awareness of detrimental behaviors that are impacting us negatively. Thus, dopamine fasting or detox refers to a mechanism which intends to prevent constant stimulation. When the brain is hypothetically overwhelmed with dopaminergic activity, it may start down regulating dopamine receptors and their effects.

Strategies used for Dopamine Detox:

• Self-awareness: Being self-aware about the problematic behaviors that needs to be addresses
• Restricting access: Limiting the time spent on that activity
• Demarcating windows for access: One can designate a particular time period where they can indulge in that activity
• Alternate activity: Engaging in an alternate activity which turns the maladaptive behavior into a positive one
• Mindfulness: Impulse control is crucial for us to be in control of the activity rather than the other way around.
• Checking for urges while stimulus prevention: Urge surfing is a practice when one witnesses their urges to appear and subside without engaging in that activity

However, since dopamine is a neurotransmitter produced in our cognitive structures it is quite impossible for an individual to have a complete dopamine detox. Although, limiting the access to maladaptive activities for a period of time might help the individual to reinforce positive ones. Moreover, for addicts refraining from social media, mindlessly viewing TV and many such activities that otherwise produce dopamine naturally, might aid in having a positive impact overall.

Dopamine Addiction:

Dopamine gives us a sense of pleasure, prompting us to pursue activities that stimulate its release. While an individual can’t become addicted to dopamine itself like a drug as it is naturally produced in our bodies, the pursuit of a dopamine rush can encourage risky behaviors. In some cases, we may even develop addictions to substances or activities that cause our dopamine levels to rise.

Although, dopamine is one of the contributing factors responsible for addiction along with genes, socio-cultural factors, personality traits like impulsivity or novelty-seeking, parenting styles and environmental stressors. An individual might develop dopamine dependence where they actively involve themselves in endeavors which exhibit dopamine release.

Methods to avoid dopamine dependence:

• Defining boundaries: Setting limits for activities that stimulate the production of dopamine and refraining from the urges to do the same is essential for establishing boundaries. One can engage in journaling in order to track their urges and usage of the substance or the time spent on the maladaptive activities.
• Relaxation techniques: Progressive muscle relaxation, visualization, box breathing, aromatherapy, yoga and meditation are self-care practices to relieve stress and practice nerve- calming activities.
• Mindfulness: It aims at achieving awareness of one’s thoughts, feelings and surroundings which enhances emotional regulation, reducing stress and anxiety and fosters peace and well-being. It’s important to stay mindful of the activities one engages in to assess whether they are leading to addictive behavior or if they are being pursued solely for the dopamine rush.

Dopamine and Online shopping:

Research suggests that the brain releases dopamine in anticipation of a reward, and unpredictability heightens this anticipation, leading to a greater dopamine release. Online shopping fosters this anticipation as customers wait for their purchases to be delivered. A study revealed that 76 percent of Americans feel more excitement receiving online orders in the mail compared to in-store purchases. Online shopping introduces more unpredictability than in-store shopping, as customers must wait for their orders to arrive, unlike the instant gratification of receiving purchases immediately in-store.

Robert Sapolsky’s experiment on the monkeys proved that dopamine is released in the anticipation of the reward. Monkeys were trained that when a light signal is witnessed, on pressing the lever, a reinforcement would be received (food treat). The graph was measured and indicated that the dopamine release is initiated by the light signal and subsides upon pressing the lever. Additionally, four Scenarios were created where the monkeys received reinforcements 25-100% of the times.

• When the monkeys received rewards 100% of the time, dopamine release was the lowest among all four scenarios. This was because the predictability was high, and the monkeys consistently expected the reward.
• When the monkeys received rewards 75% or 25% of the time, they either rarely expected a reinforcement in the 25% case or almost always anticipated it in the 75% case. Despite the variation, the rewards were still somewhat predictable, thus the dopamine release was between the levels observed in the 50% and 100% scenarios.
• When the monkeys received food treats 50% of the time, the unpredictability was greatest among the four scenarios. Consequently, dopamine release was at its highest compared to the other situations.

Conclusion

Maintaining proper dopamine levels helps a person stay focused, motivated, and happy, while imbalances contribute to the development of various disorders like clinical depression, eating disorders, substance-use disorders, Parkinson’s disease, schizophrenia and sleep disturbances. dopamine agonists, antagonists, and reuptake inhibitors are commonly used in treatment of the same.

A diet rich in tyrosine and magnesium can naturally boost dopamine levels in the body. Additionally, participating in pleasurable activities such as listening to music, exercising, or eating sweets releases dopamine in the brain. This neurotransmitter plays a key role in regulating metabolism, sleep, motivation, reward, and the satisfaction of needs. Dopamine is released during high-risk activities like gambling, internet-use, substance-abuse, impulsive shopping and the individual gets prone to being an addict towards these substances or activities.

Although, dopamine merely is not the contributing factor for addiction and the same is associated with many casual factors. Furthermore, in order to prevent dopamine dependence, an individual should engage in response prevention, demarcate their boundaries and limit the time spent on the maladaptive activities replacing them with positive behavior and activities. Thus, indulging in self-care activities like journaling, aromatherapy, yoga and meditation aid in improving dopamine levels, enhancing concentration and fostering overall wellbeing.