Zeroing In on Dopamine


Study identifies the molecular machinery responsible for dopamine release in the brain

Super-resolution microscopy reveals active release sites (green) on dopamine neurons (purple) for the first time.

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.

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 the 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.”

How To Supercharge Your Dopamine Levels To Never Feel Sad, Stressed Or Depressed Again


Our brain releases a neurotransmitter, dopamine, which is crucial for numerous essential bodily functions. Dopamine is great for the following body functions:

– Regulating movement
– Controlling the center of pleasure and reward in the brain
– Improving the cognitive functions (knowledge, attention, memory, decision-making, evaluation, problem solving)
– Regulating the secretion of prolactin

Since it is extremely important for our wellbeing and happiness, the reduced levels of dopamine lead to various health issues, such as depression, sadness, negativity and various emotional troubles.

Fortunately, there are 10 effective ways to raise the dopamine levels in the body, without using medications:

1. Exercise

The exercise of every kind raises the levels of dopamine, serotonin, and endorphin. Regular exercise provides happiness, strengthens the body, reduces stress. Try the plank.

2. Avoid Addictions

Addiction to alcohol, drugs, gambling, and even shopping, provide an instant pleasure, but it is not a permanent solution. Additions only temporarily satisfy our needs.

Moreover, addictions alter our lifestyle in favor of the source of the addiction, and it is a wicked cycle. Therefore, you should try and lower the risk of developing addictions, enjoy life, and find things that provide deeper calmness and happiness. Also, it is of great importance to work a job you enjoy.

3. Detoxification

Make sure you regularly detoxify your system, as the accumulation of toxins and bacteria in the body prevents the dopamine production and weakens the immunity. Try this one.

4. Increase Tyrosine

Tyrosine is one of the 22 essential amino acids used for the creation of proteins. It is actually the most important chemical for the dopamine production of dopamine.

Besides dopamine, it also has the potential to elevate norepinephrine levels. In order to raise its levels in the body, you should consume green tea, watermelon, almonds, bananas, avocados, and dark chocolate.

5. Music

Dopamine levels are also increased through listening to music, even though it may be short-term. Therefore, use music as a common way to raise dopamine levels. And by the way playing an instrument makes you smarter (science reveals).

6. Organize your life

The levels of dopamine are raised in the case of organized small daily tasks, even though they are hard at times. You should write your tasks down on a piece of paper, and check them off. In this way, you will be satisfied as you note that you finish them one by one.

The Principles of Self-Management state that if a task represents a change of 25% (or bigger change) in the routine, you will feel unable to finish it, and often ends up with a self-sabotage or giving up.

If the task changes 10% of your routine, you will succeed to complete it, as you will believe it is small. Therefore, balance tasks to be 10 and 25% of new behaviors, in order to try new and challenging things, but still not too difficult to complete.

7. Creativity

The levels of dopamine in the brain are also elevated with a creative activity. This will also keep you focused. You do not need to become a world-known artist but try dancing, singing, writing, sculpturing, painting, drawing, cooking, knitting, making crafts, and auto repair, and you will feel much better right away.

8. Get a Streak Going

In this sense, “streak” will mean a visual reminder of the number of times in a row you do something. This is similar to organizing the tasks, and accomplishing them. This will raise the levels of dopamine, and make you happier and satisfied. You should use a calendar, written your goals, and plan when to complete them. As soon as you finish the task, mark it off on your calendar. Yet, the drawback of the ‘streak’ is routine, so you should find a way to enhance the performance.

9. Supplementation

Dopamine levels can also be raised through supplementation, such as:

  • Curcumin, the active ingredient in turmeric, effectively increases dopamine in the brain.
  • Ginkgo Biloba has a potential to raise dopamine levels as well.
  • Acetyl-l-tyrosine is a building block of dopamine, so a healthy dose of it supports the production of dopamine in the brain.
  • L-theanine increases numerous neurotransmitters in the brain, including dopamine. Green tea is a rich source of l-theanine.

10. Meditation

Meditation raises the levels of dopamine in a different way that cardio exercises. It improves your mood, creates mental energy, and relaxes the mind. Meditation is an efficient way to reduce stress on a daily basis. Harvard MRI studies proved that meditation literally rebuilds your brain gray matter in 8 weeks!

How To Supercharge Your Dopamine Levels To Never Feel Sad, Stressed Or Depressed Again


Our brain releases a neurotransmitter, dopamine, which is crucial for numerous essential bodily functions. Dopamine is great for the following body functions:

– Regulating movement
– Controlling the center of pleasure and reward in the brain
– Improving the cognitive functions (knowledge, attention, memory, decision-making, evaluation, problem solving)
– Regulating the secretion of prolactin

Since it is extremely important for our wellbeing and happiness, the reduced levels of dopamine lead to various health issues, such as depression, sadness, negativity and various emotional troubles.

Fortunately, there are 10 effective ways to raise the dopamine levels in the body, without using medications:

1. EXERCISE

The exercise of every kind raises the levels of dopamine, serotonin, and endorphin. Regular exercise provides happiness, strengthens the body, reduces stress. Try the plank.

2. AVOID ADDICTIONS

Addiction to alcohol, drugs, gambling, and even shopping, provide an instant pleasure, but it is not a permanent solution. Additions only temporarily satisfy our needs.

Moreover, addictions alter our lifestyle in favor of the source of the addiction, and it is a wicked cycle. Therefore, you should try and lower the risk of developing addictions, enjoy life, and find things that provide deeper calmness and happiness. Also, it is of great importance to work a job you enjoy.

3. DETOXIFICATION

Make sure you regularly detoxify your system, as the accumulation of toxins and bacteria in the body prevents the dopamine production and weakens the immunity. Try this one.

4. INCREASE TYROSINE

Tyrosine is one of the 22 essential amino acids used for the creation of proteins. It is actually the most important chemical for the dopamine production of dopamine.

Besides dopamine, it also has the potential to elevate norepinephrine levels. In order to raise its levels in the body, you should consume green tea, watermelon, almonds, bananas, avocados, and dark chocolate.

5. MUSIC

Dopamine levels are also increased through listening to music, even though it may be short-term. Therefore, use music as a common way to raise dopamine levels. And by the way playing an instrument makes you smarter (science reveals).

6. ORGANIZE YOUR LIFE

The levels of dopamine are raised in the case of organized small daily tasks, even though they are hard at times. You should write your tasks down on a piece of paper, and check them off. In this way, you will be satisfied as you note that you finish them one by one.

The Principles of Self-Management state that if a task represents a change of 25% (or bigger change) in the routine, you will feel unable to finish it, and often ends up with a self-sabotage or giving up.

If the task changes 10% of your routine, you will succeed to complete it, as you will believe it is small. Therefore, balance tasks to be 10 and 25% of new behaviors, in order to try new and challenging things, but still not too difficult to complete.

7. CREATIVITY

The levels of dopamine in the brain are also elevated with a creative activity. This will also keep you focused. You do not need to become a world-known artist but try dancing, singing, writing, sculpturing, painting, drawing, cooking, knitting, making crafts, and auto repair, and you will feel much better right away.

8. GET A STREAK GOING

In this sense, “streak” will mean a visual reminder of the number of times in a row you do something. This is similar to organizing the tasks, and accomplishing them. This will raise the levels of dopamine, and make you happier and satisfied. You should use a calendar, written your goals, and plan when to complete them. As soon as you finish the task, mark it off on your calendar. Yet, the drawback of the ‘streak’ is routine, so you should find a way to enhance the performance.

9. SUPPLEMENTATION

Dopamine levels can also be raised through supplementation, such as:

  • Curcumin, the active ingredient in turmeric, effectively increases dopamine in the brain.
  • Ginkgo Biloba has a potential to raise dopamine levels as well.
  • Acetyl-l-tyrosine is a building block of dopamine, so a healthy dose of it supports the production of dopamine in the brain.
  • L-theanine increases numerous neurotransmitters in the brain, including dopamine. Green tea is a rich source of l-theanine.

Note: consult a doctor before using any of the above

10. MEDITATION

Meditation raises the levels of dopamine in a different way that cardio exercises. It improves your mood, creates mental energy, and relaxes the mind. Meditation is an efficient way to reduce stress on a daily basis. Harvard MRI studies proved that meditation literally rebuilds your brain gray matter in 8 weeks!

Scientists identify brain molecule that triggers schizophrenia-like behaviors, brain changes


Scientists at The Scripps Research Institute (TSRI) have identified a molecule in the brain that triggers schizophrenia-like behaviors, brain changes and global gene expression in an animal model. The research gives scientists new tools for someday preventing or treating psychiatric disorders such as schizophrenia, bipolar disorder and autism.

“This new model speaks to how schizophrenia could arise before birth and identifies possible novel drug targets,” said Jerold Chun, a professor and member of the Dorris Neuroscience Center at TSRI who was senior author of the new study.

The findings were published April 7, 2014, in the journal Translational Psychiatry.

What Causes Schizophrenia?

According to the World Health Organization, more than 21 million people worldwide suffer from schizophrenia, a severe psychiatric disorder that can cause delusions and hallucinations and lead to increased risk of suicide.

Although psychiatric disorders have a genetic component, it is known that environmental factors also contribute to disease risk. There is an especially strong link between psychiatric disorders and complications during gestation or birth, such as prenatal bleeding, low oxygen or malnutrition of the mother during pregnancy.

In the new study, the researchers studied one particular known risk factor: bleeding in the brain, called fetal cerebral hemorrhage, which can occur in utero and in premature babies and can be detected via ultrasound.

In particular, the researchers wanted to examine the role of a lipid called lysophosphatidic acid (LPA), which is produced during hemorrhaging. Previous studies had linked increased LPA signaling to alterations in architecture of the fetal brain and the initiation of hydrocephalus (an accumulation of brain fluid that distorts the brain). Both types of events can also increase the risk of psychiatric disorders.

“LPA may be the common factor,” said Beth Thomas, an associate professor at TSRI and co-author of the new study.

Mouse Models Show Symptoms

To test this theory, the research team designed an experiment to see if increased LPA signaling led to schizophrenia-like symptoms in animal models.

Hope Mirendil, an alumna of the TSRI graduate program and first author of the new study, spearheaded the effort to develop the first-ever animal model of fetal cerebral hemorrhage. In a clever experimental paradigm, fetal mice received an injection of a non-reactive saline solution, blood serum (which naturally contains LPA in addition to other molecules) or pure LPA.

The real litmus test to show if these symptoms were specific to psychiatric disorders, according to Mirendil, was “prepulse inhibition test,” which measures the “startle” response to loud noises. Most mice—and humans—startle when they hear a loud noise. However, if a softer noise (known as a prepulse) is played before the loud tone, mice and humans are “primed” and startle less at the second, louder noise. Yet mice and humans with symptoms of schizophrenia startle just as much at loud noises even with a prepulse, perhaps because they lack the ability to filter sensory information.

Indeed, the female mice injected with serum or LPA alone startled regardless of whether a prepulse was placed before the loud tone.

Next, the researchers analyzed brain changes, revealing schizophrenia-like changes in neurotransmitter-expressing cells. Global gene expression studies found that the LPA-treated mice shared many similar molecular markers as those found in humans with schizophrenia. To further test the role of LPA, the researchers used a molecule to block only LPA signaling in the brain.

This treatment prevented schizophrenia-like symptoms.

Implications for Human Health

This research provides new insights, but also new questions, into the developmental origins of psychiatric disorders.

For example, the researchers only saw symptoms in female mice. Could schizophrenia be triggered by different factors in men and women as well?

“Hopefully this animal model can be further explored to tease out potential differences in the pathological triggers that lead to disease symptoms in males versus females,” said Thomas.

In addition to Chun, Thomas and Mirendil, authors of the study, “LPA signaling initiates schizophrenia-like brain and behavioral changes in a mouse model of prenatal brain hemorrhage,” were Candy De Loera of TSRI; and Kinya Okada and Yuji Inomata of the Mitsubishi Tanabe Pharma Corporation.

Dopamine helps with math rules as well as mood


The chemical messenger dopamine – otherwise known as the happiness hormone – is important not only for motivation and motor skills. It seems it can also help neurons with difficult cognitive tasks. Torben Ott, Simon Jacob and Professor Andreas Nieder of Tübingen’s Institute for Neurobiology have demonstrated for the first time how dopamine influences brain cells while processing rules. You can read the study in full in the early online edition of Neuron.

The effects of dopamine become very clear when the brain gets too little of it, as is the case with Parkinson’s disease. A dopamine imbalance leads to varied neurological disruptions – particularly movement – but also mental abilities. Our key cognitive center, the prefrontal cortex, which we use for abstract thought, rule-based decisions and logical conclusions, is intensively supplied with dopamine. Despite its major medical significance, we know little about dopamine’s effects on information processing by neurons in the healthy brain.

To test this, the researchers trained rhesus monkeys to solve “greater than” and “less than” math problems. From other recent studies, the researchers knew that certain neurons in the prefrontal cortex answer such questions – one half of these “rule cells” was only activated when the “greater than” rule applied, and the other half was only activated when the “less than” rule applied.

Meanwhile, physiologically small amounts of various substances were being discharged near the relevant cells. These substances can have the same effect as dopamine – or the opposite effect – and could be adsorbed by dopamine-sensitive neurons. The surprising result was that stimulation of the allowed the “rule cells” to perform better and to more clearly distinguish between the “greater than” and “less than” rules. Dopamine had a positive effect on the “rule cells'” quality of work.

The study provides new insight into how dopamine influences abstract thought processes needed, for instance, to apply simple mathematical rules. “With these findings, we are just starting to understand how nerve cells in the prefrontal cortex produce complex, goal-directed behavior,” says Ott. Along with a better understanding of the foundations of in this important part of the brain, the results could have medical significance. “These new insights help us to better interpret the effects of certain medicines which may be used for instance in cases of severe psychological disturbance,” says Professor Nieder, “because such medications influence the balance in the in ways we do not understand well to date.”

Simple Test May Help Gauge Dopamine Loss in Parkinson’s.


The Triplets Learning Task (TLT) may help determine the extent of dopamine loss in patients with Parkinson’s disease (PD), results of a pilot study hint.

The TLT tests implicit learning, a type of learning that occurs without awareness or intent and that relies on the caudate nucleus, an area of the brain affected by dopamine loss.

The test is a sequential learning task that doesn’t require complex motor skills, which tend to decline in people with PD. In the TLT, participants see 4 open circles, see 2 red dots appear, and are asked to respond when they see a green dot appear. Unbeknownst to them, the authors note, the location of the first red dot predicts the location of the green target. Participants learn implicitly where the green target will appear, and they become faster and more accurate in their responses.

Katherine R. Gamble, psychology PhD student at Georgetown University in Washington, DC, and colleagues had 27 patients with mild to moderate PD receiving dopaminergic medication and 27 healthy controls matched for age and education take the TLT on several occasions.

Patients with PD implicitly learned the dot pattern with training, as did controls, but a loss of dopamine appeared to “negatively impact” that learning compared with healthy older adults, Gamble noted in an interview with Medscape Medical News.

“Their performance began to decline toward the end of training, suggesting that people with Parkinson’s disease lack the neural resources in the caudate, such as dopamine, to complete the learning task,” she added in a conference statement.

Gamble reported the findings here at Neuroscience 2013, the annual meeting of the Society for Neuroscience.

Implicit Learning

In this study, participants responded to 6 “epochs” of the TLT, for a total of 1500 trials. All patients had been diagnosed with PD by a neurologist, and all were receiving treatment with anti-PD medication when they took the test.

Their results showed “significant implicit sequence learning” on the TLT test, the researchers report. Learning increased over the first 5 epochs of training, they note; patients continued to respond more quickly to high- vs low-probability triplets, but this plateaued between periods 5 and 6.

“We suggest that in people with PD, learning is intact early in training because less affected regions of the brain (eg, the hippocampus) can support learning,” they conclude. “However, PD-related dopamine deficits appear later in training when the caudate becomes more important.”

The TLT “may be a noninvasive way to evaluate the level of dopamine deficiency in PD patients, and which may lead to future ways to improve clinical treatment of PD patients,” said Steven E. Lo, MD, associate professor of neurology at Georgetown University Medical Center and a coauthor of the study, in a statement.

The researchers are now testing how implicit learning may differ by different PD stages and drug doses.

Evaluating Dopamine Deficiency

Asked to comment on this pilot study, Lidia Gardner, PhD, assistant professor, Department of Neurology, University of Tennessee Health Science Center in Memphis, said the “simple implicit learning test might be potentially a useful tool for neuropsychologists. I would like to know if there is any correlation between the disease progression and the time required for TLT training.”

However, she told Medscape Medical News, “Until a strong correlation is established, most physicians would shy away from using it as a diagnostic tool for the loss of dopamine neurons. However, in addition to other clinical tests it could be useful.”

“Currently, the loss of dopamine neurons can be visualized with PET [positron emission tomography] using 18F-DOPA or other radio-tracers. This technique can give a relatively close assessment of dopamine neurons in PD patients. A simple and inexpensive test (in comparison to PET or SPECT [single-photon emission computed tomography]) is always welcome in healthcare administration,” Dr. Gardner said.

Get Off the Pot.


Researchers demonstrate the successful treatment of marijuana abuse in rats and monkeys.

A drug that increases levels of a naturally occurring chemical may help marijuana users kick the habit, according to new research published this week (October 13) in Nature Neuroscience. In rats, the drug, called Ro 61-8048, boosted brain levels of kynurenic acid dosed with THC, marijuana’s active ingredient, which subsequently diminished dopamine-driven neural activity associated with pleasure. In monkeys, the same treatment reduced voluntary use of THC by 80 percent.

“The really interesting finding is that when we looked at behavior, simply increasing kynurenic acid levels totally blocked the abuse potential and the chance of relapse,” coauthor Robert Schwarcz, a neuroscientist at the University of Maryland, told Smithsonian.com. “It’s a totally new approach to affecting THC function.”

Though marijuana may not have serious long-term consequences, and may even hold potential in treating various medical maladies, it is commonly used as a recreational drug, and some people who abuse it show signs of addiction to the substance. This addiction is believed to stem from THC’s ability to activate the pleasure circuitry of the brain, increasing levels of dopamine and eliciting feelings of happiness. Kynurenic acid can also mediate dopamine-regulated brain activity, and was thus a top target of Schwarcz and his colleagues as they looked for ways to inhibit THC’s euphoric effects.

Indeed, dosing rats with Ro 61-8048 caused kynurenic acid levels to rise, after which THC no longer elicited the dopamine-driven brain activity in the reward centers of the brain, including the nucleus accumbens. It seemed that kynurenic acid was literally blocking the brain’s dopamine receptors, thereby decreasing the pleasurable feelings normally elicited by THC. As a result of the treatment, both rats and monkeys with the ability to self-dose with THC reduced their drug intake by about 80 percent.

“Currently, we’re doing some experiments with nicotine abuse, and there’s some very interesting preliminary data indicating it may work the same way,” Schwarcz told Smithsonian.com.

Septic Shock? Reach for Norepinephrine After Fluid Resuscitation.


A meta-analysis shows that dopamine is associated with increased risk for death and arrhythmic events compared with norepinephrine.

Although current guidelines recommend either dopamine or norepinephrine as the vasopressors of choice for septic shock, a recent meta-analysis of six interventional studies suggested that norepinephrine is the superior agent (JW Emerg Med Apr 22 2011). Investigators conducted a meta-analysis of the same six interventional studies — excluding patients with nonseptic shock — and five observational studies; the analysis involved a total of 2768 adult patients.

Observational studies showed significant heterogeneity in results overall and no difference in mortality between patients treated with dopamine and those treated with norepinephrine. After exclusion of one trial that accounted for the heterogeneity, dopamine was associated with an increased risk for death at 28 days over norepinephrine (relative risk, 1.23). Interventional trials were homogeneous and likewise showed a significantly increased risk for death with dopamine use (RR, 1.12). Two interventional studies that reported arrhythmic events showed a significant increase in these events in the dopamine groups (RR, 2.34).

An editorialist suggests that dopamine, a more powerful β-agonist than norepinephrine, could still be considered in patients with septic shock, hypotension (systolic blood pressure <90 mm Hg), and either a low cardiac index (<2.5 L/minute/m2) or low heart rate (<90 beats per minute).

Comment: This study supports norepinephrine as the vasopressor of choice for adult patients with septic shock. Dopamine is relegated to a secondary role, perhaps to be used when cardiac output is insufficient despite optimal use of norepinephrine.

Source: Journal Watch Emergency Medicine

 

Norepinephrine Outperforms Dopamine in Adults with Septic Shock.


Use of norepinephrine was associated with a 9% reduction in mortality compared with dopamine.

According to the Surviving Sepsis Campaign guidelines, norepinephrine or its precursor, dopamine, are both recommended as first-line treatments to improve organ perfusion in patients with septic shock. To determine which vasopressor is better, researchers conducted a meta-analysis of six randomized trials that compared the two agents in patients with septic shock and that reported in-hospital or 28-day mortality.

The trials included a total of 995 patients randomized to norepinephrine and 1048 randomized to dopamine. Overall, mortality was significantly lower in the norepinephrine group than in the dopamine group (48% vs. 53%). Arrhythmias were significantly less common with norepinephrine than with dopamine (relative risk, 0.43).

Comment: This study suggests that norepinephrine is superior to dopamine for adult patients with refractory septic shock. The finding that dopamine is associated with more arrhythmias might explain the higher mortality, as arrhythmias can impair cardiac function, thereby leading to worse outcomes.

Source: Journal Watch Emergency Medicine.